biological and medical physics, biomedical engineering

For further volumes: http://www.springer.com/series/3740

biological and medical physics, biomedical engineering

The elds of biological and medical physics and biomedical engineering are broad, multidisciplinary and dynamic. They lie at the crossroads of frontier research in physics, biology, chemistry, and medicine. The Biological and Medical Physics, Biomedical Engineering Series is intended to be comprehensive, covering a broad range of topics important to the study of the physical, chemical and biological sciences. Its goal is to provide scientists and engineers with textbooks, monographs, and reference works to address the growing need for information. Books in the series emphasize established and emergent areas of science including molecular, membrane, and mathematical biophysics; photosynthetic energy harvesting and conversion; information processing; physical principles of genetics; sensory communications; automata networks, neural networks, and cellular automata. Equally important will be coverage of applied aspects of biological and medical physics and biomedical engineering such as molecular electronic components and devices, biosensors, medicine, imaging, physical principles of renewable energy production, advanced prostheses, and environmental control and engineering.

Editor-in-Chief:
Elias Greenbaum, Oak Ridge National Laboratory, Oak Ridge, Tennessee, USA

Editorial Board:
Masuo Aizawa, Department of Bioengineering, Tokyo Institute of Technology, Yokohama, Japan Olaf S. Andersen, Department of Physiology, Biophysics & Molecular Medicine, Cornell University, New York, USA Robert H. Austin, Department of Physics, Princeton University, Princeton, New Jersey, USA James Barber, Department of Biochemistry, Imperial College of Science, Technology and Medicine, London, England Howard C. Berg, Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts, USA Victor Bloomf ield, Department of Biochemistry, University of Minnesota, St. Paul, Minnesota, USA Robert Callender, Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York, USA Steven Chu, Lawrence Berkeley National Laboratory, Berkeley, California, USA Louis J. DeFelice, Department of Pharmacology, Vanderbilt University, Nashville, Tennessee, USA Johann Deisenhofer, Howard Hughes Medical Institute, The University of Texas, Dallas, Texas, USA George Feher, Department of Physics, University of California, San Diego, La Jolla, California, USA Hans Frauenfelder, Los Alamos National Laboratory, Los Alamos, New Mexico, USA Ivar Giaever, Rensselaer Polytechnic Institute, Troy, New York, USA Sol M. Gruner, Cornell University, Ithaca, New York, USA Judith Herzfeld, Department of Chemistry, Brandeis University, Waltham, Massachusetts, USA

Mark S. Humayun, Doheny Eye Institute, Los Angeles, California, USA Pierre Joliot, Institute de Biologie Physico-Chimique, Fondation Edmond de Rothschild, Paris, France Lajos Keszthelyi, Institute of Biophysics, Hungarian Academy of Sciences, Szeged, Hungary Robert S. Knox, Department of Physics and Astronomy, University of Rochester, Rochester, New York, USA Aaron Lewis, Department of Applied Physics, Hebrew University, Jerusalem, Israel Stuart M. Lindsay, Department of Physics and Astronomy, Arizona State University, Tempe, Arizona, USA David Mauzerall, Rockefeller University, New York, New York, USA Eugenie V. Mielczarek, Department of Physics and Astronomy, George Mason University, Fairfax, Virginia, USA Markolf Niemz, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany V. Adrian Parsegian, Physical Science Laboratory, National Institutes of Health, Bethesda, Maryland, USA Linda S. Powers, University of Arizona, Tucson, Arizona, USA Earl W. Prohofsky, Department of Physics, Purdue University, West Lafayette, Indiana, USA Andrew Rubin, Department of Biophysics, Moscow State University, Moscow, Russia Michael Seibert, National Renewable Energy Laboratory, Golden, Colorado, USA David Thomas, Department of Biochemistry, University of Minnesota Medical School, Minneapolis, Minnesota, USA

Heinz Fabian Dieter Naumann

Editors

Protein Folding and Misfolding

Shining Light by Infrared Spectroscopy
With 108 Figures

123

Editors:

Dr. Heinz Fabian Professor Dr. Dieter Naumann

Robert Koch Institut Nordufer 20, 13353 Berlin, Germany E-mail: fabianH@rki.de, naumannD@rki.de

Biological and Medical Physics, Biomedical Engineering ISSN 1618-7210 ISBN 978-3-642-22229-0 e-ISBN 978-3-642-22230-6 DOI 10.1007/978-3-642-22230-6 Springer Heidelberg Dordrecht London New York
Library of Congress Control Number: 2011937438 Springer-Verlag Berlin Heidelberg 2012 This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specif ically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microf ilm or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1965, in its current version, and permission for use must always be obtained from Springer. Violations are liable to prosecution under the German Copyright Law. The use of general descriptive names, registered names, trademarks, etc. in this publication does not imply, even in the absence of a specif ic statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Cover design: eStudio Calamar Steinen Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com)

Preface

The progress in understanding protein folding and misfolding is primarily due to the development of biophysical methods, which permit to probe conformational changes with high kinetic and structural resolution. A whole battery of techniques is being used to address the fundamental problems of protein folding and misfolding. The most common approaches rely on rapid-mixing methods to initiate the folding event via a sudden change in solvent conditions. Traditionally, techniques such as uorescence, circular dichroism or visible absorption spectroscopy are applied to study the processes. In contrast to these techniques, infrared spectroscopy came into play only very recently. The signicant progress made in this eld to date permits to follow folding events over the timescale from picoseconds to minutes with high structural resolution. The aim of this unique book is to provide an overview of the latest developments and applications as seen by pioneers in this burgeoning eld. The various chapters present representative examples on the sort of information which infrared techniques can provide and how this information is extracted from the experimental data. The discussion of the state-of-art technology, data evaluation strategies and representative applications on protein folding and misfolding should help the readers to estimate whether their particular systems are appropriate to be studied by infrared spectroscopy, and to assess the specic advantages the various infrared techniques have. This book contains nine chapters. The introductory chapter by Gareth Morgan and Sheena Radford focuses on the array of experimental methods that are presently applied to the key questions of how folding, misfolding and aggregation of proteins are linked, both in vitro and in the environment of the cell. The second chapter by Joseph Brauner and Richard Mendelsohn presents a semi-empirical method of simulating the experimental amide I contour of a protein or peptide molecule whose atomic coordinates are available, and discusses the correlations between the amide I contour and the secondary structure of a protein. The adaptation of conventional mixing and temperature-jump technologies to the specic requirements of time-resolved FTIR spectroscopy, which enable to explore protein folding and misfolding events on the millisecond-to-minute timescale, together with

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representative results on different proteins, is then described by Heinz Fabian and Dieter Naumann. The fourth chapter by Satoshi Takahashi and Tetsunari Kimura gives an overview on time-resolved FTIR spectroscopy based on continuous-ow rapid-mixing set-ups, which allow to follow protein folding events in the submillisecond-to-second time range. The authors describe practical issues in applying their devices to explore mechanism of secondary structure formation and protein main chain dehydration. Chapter 5 by Roland Winter and co-workers reports on pressure changes as an alternative trigger to unfold or refold proteins and to induce disaggregation of misfolded species. After describing the experimental techniques, examples of pressure-induced un- and refolding reactions of proteins as well as studies on enzyme reactions are presented. The use of laser-induced temperaturejump IR spectroscopy as a method to study -helix and -sheet formation in the nanosecond-to-microsecond time range is presented by Karin Hauser, with emphasis on strategies to obtain insights into folding mechanism on the level of single amino acid residues. The seventh chapter by Wolfgang Zinth and Josef Wachtveitl demonstrates that photo-switches incorporated into suitably designed amino acid sequences open up numerous new applications by applying light as trigger to initiate peptide folding. Their pioneering investigations on selected lighttriggered peptides demonstrate ultrafast folding reactions, and show that these processes may span the range between picoseconds and tens of microseconds. Another way to trigger unfolding and misfolding events by light is the use of caged compounds, which is described next by Andreas Barth and co-workers with special focus on the use of caged protons for time-resolved infrared spectroscopic experiments. The light-induced release of protons generates a pH jump much more rapidly than any conventional mixing technique, thus paving the way for investigating early events of aggregation processes of peptides or proteins. The nal chapter by Martin Zanni and co-workers illustrates that two-dimensional infrared spectroscopy combined with isotope labelling is an elegant and powerful tool to obtain residue-specic structural information on folding and aggregation processes of peptides and proteins. A mathematical formalism to guide the interpretation of one- and two-dimensional IR spectra of amyloid brils is presented, which enables the design of the best isotope labelling scheme of the peptide. The chapter ends with explanatory experiments, demonstrating the specic power of the two-dimensional IR approach. This book is the result of the work of many colleagues who generously agreed to contribute to this book by taking time away from their other responsibilities. We wish to thank all the authors for their extremely valuable contributions. We hope that their ideas and experiences will be of interest not only for those readers already familiar with infrared spectroscopic techniques, but also inspire other colleagues in the protein community to take advantage of the possibilities described herein for

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their particular research in the future. Special thanks go to our co-worker Angelika Brauer for her great help and continuous encouragement during the technical preparation of the book chapters. Berlin, Germany July 2011 Heinz Fabian Dieter Naumann

Contents

Linked Landscapes and Conformational Conversions: How Proteins Fold and Misfold . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . Gareth J. Morgan and Sheena E. Radford 1.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 1.2 The Unfolded Ensemble Under Native Conditions .. . . . . . . . . . . . . . . . . . . 1.3 Folding and Misfolding Intermediates . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 1.4 Protobrils, Oligomers and Toxicity . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 1.5 Amyloid Structure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 1.6 From the Test Tube to the Cell . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 1.7 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . .

1 1 4 6 8 9 11 13 13

2 A Quantitative Reconstruction of the Amide I Contour in the IR Spectra of Peptides and Proteins: From Structure to Spectrum .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . Joseph W. Brauner and Richard Mendelsohn 2.1 The Approach to Simulation of the Amide I Contour .. . . . . . . . . . . . . . . . 2.1.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 2.1.2 Historical Background .. . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 2.1.3 Normal Coordinate Calculations . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 2.1.4 Ab Initio Force Field Calculations . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 2.1.5 The Modied GF Matrix Method .. . . . . . . . .. . . . . . . . . . . . . . . . . . . . 2.1.6 Constructing the G and F Matrices in the Coupled Oscillators of One Kind Method . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 2.1.7 Simulating the Amide I Contour .. . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 2.2 Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 2.2.1 Isotopic Labeling . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 2.2.2 Modeling the Early Stages of Thermal Denaturation . . . . . . . . . 2.2.3 Amide I Structure-Frequency Correlations in Globular Proteins . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 2.2.4 IRRAS Simulations .. . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . .

17 17 17 18 19 20 21 22 31 32 33 39 41 45
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2.3 Conclusions and Future Prospects.. . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 3 Millisecond-to-Minute Protein Folding/Misfolding Events Monitored by FTIR Spectroscopy.. . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . Heinz Fabian and Dieter Naumann 3.1 General Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 3.2 FTIR Spectroscopy, Experimental Aspects . . . . . . . .. . . . . . . . . . . . . . . . . . . . 3.2.1 Proteins in Aqueous Solutions . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 3.2.2 Measurements in D2 O . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 3.2.3 FTIR Spectra of Chemical Denaturants . . .. . . . . . . . . . . . . . . . . . . . 3.3 Kinetic FTIR Experiments Applying Rapid Mixing and Temperature-Jump Approaches .. . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 3.3.1 Rapid-Scan FTIR Spectroscopy: Advantages and Limitations . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 3.3.2 Design and Operation of a Stopped-Flow Apparatus for Measurements in Heavy Water . . . . . . . . . . . . . . . . . 3.3.3 A Stopped-Flow Apparatus for Measurements of H2 O-Protein Solutions .. . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 3.3.4 T-Jump Experiments in Heavy Water . . . . . .. . . . . . . . . . . . . . . . . . . . 3.4 Examples of Applying T-Jumps onto a Protein Solution.. . . . . . . . . . . . . 3.4.1 Refolding of Wild-Type Ribonuclease T1 and Some of Its Mutants. . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 3.4.2 Unfolding of the -Cro Repressor . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 3.5 Examples Making Use of Rapid-Mixing Methods . . . . . . . . . . . . . . . . . . . . 3.5.1 Refolding of -Lactalbumin Studied by Stopped-Flow Infrared Spectroscopy After a pH-Jump . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 3.5.2 Misfolding of 2 -Microglobulin . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 3.5.3 The -to- Conversion Process of the Prion Protein . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 4 Watching Dynamical Events in Protein Folding in the Time Domain from Submilliseconds to Seconds: Continuous-Flow Rapid-Mixing Infrared Spectroscopy . . . . . . . . . . . . . . . . Satoshi Takahashi and Tetsunari Kimura 4.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 4.2 The Collapse and Search Mechanism of Protein Folding .. . . . . . . . . . . . 4.2.1 The Protein Folding Mechanism Depends on the Chain Length . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 4.2.2 Kinetic Investigation of Protein Folding for Intermediate Proteins . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 4.3 Development of Continuous-Flow Time-Resolved Infrared Spectrometer .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 4.3.1 Comparison of Different Methods for Triggering Protein Folding Events . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . .

50 51 53 53 55 55 56 60 61 61 62 63 64 66 66 72 74

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4.3.2 Development of a Continuous-Flow Cell with a T-Shaped Flow Channel.. . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 4.3.3 Construction of the Time-Resolved Spectrometer Based on Infrared Microscopy . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 4.4 Practical Issues for Kinetic Infrared Investigations of Protein Folding .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 4.4.1 Selection of the Initial Unfolded State . . . . .. . . . . . . . . . . . . . . . . . . . 4.4.2 Suppression of the Aggregate Formation ... . . . . . . . . . . . . . . . . . . . 4.4.3 Method of Spectral Analysis . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 4.5 Application to Protein Folding . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 4.5.1 Pioneering Investigations of Rapid-Mixing Infrared Spectroscopy . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 4.5.2 Apomyoglobin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 4.5.3 Single-Chain Monellin . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 4.6 Summary and Perspective . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 5 High-Pressure Vibrational Spectroscopy Studies of the Folding, Misfolding and Amyloidogenesis of Proteins .. . . . . . . . . . . Roland Winter, Matthias P hse, and Jonas Markgraf u 5.1 Introduction to High-Pressure Bioscience . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 5.2 Fundamental Concepts: Stability Diagram of Proteins .. . . . . . . . . . . . . . . 5.3 Experimental Methods .. . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 5.3.1 High-Pressure FTIR Spectroscopy .. . . . . . . .. . . . . . . . . . . . . . . . . . . . 5.3.2 Diamond Anvil Cell Technology.. . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 5.3.3 Pressure Calibrants for Infrared Spectroscopy . . . . . . . . . . . . . . . . 5.4 Examples of Pressure Studies on Proteins and Polymers . . . . . . . . . . . . . 5.4.1 Pressure-Induced Protein un- and Refolding Reactions . . . . . . 5.4.2 Protein Folding Kinetics. . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 5.4.3 Pressure-Assisted Cold Denaturation of Proteins . . . . . . . . . . . . . 5.4.4 Pressure Effects on Oligomeric Proteins and Chaperones . . . . 5.4.5 Cosolvent Effects . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 5.4.6 Aggregation/Fibrillation Reactions of Proteins . . . . . . . . . . . . . . . 5.4.7 Enzymatic Reactions . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 5.4.8 Synthetic Polymers as Protein Mimetics . .. . . . . . . . . . . . . . . . . . . . 5.5 Conclusions and Outlook .. . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 6 Dynamics of -Helix and -Sheet Formation Studied by Laser-Induced Temperature-Jump IR Spectroscopy .. . . . . . . . . . . . . . . . Karin Hauser 6.1 Peptide Folding Dynamics .. . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 6.1.1 Secondary-Structure Formation .. . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 6.1.2 The Amide I Band as Structural Probe . . . .. . . . . . . . . . . . . . . . . . . . 6.1.3 Equilibrium vs. Kinetic Data . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 6.1.4 Rate Constants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . .

95 98 101 101 101 102 103 103 104 107 110 113 117 117 119 120 120 122 123 124 124 127 130 132 133 135 138 139 143 144 147 147 147 148 149 150

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6.2 Laser-Induced T-Jump Technique .. . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 6.2.1 Generation of the Heating Pulse . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 6.2.2 Photo-Acoustic Effects, Cavitation and Thermal Lensing .. . . 6.2.3 Experimental Setup .. . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 6.3 T-Jump Relaxation Kinetics . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 6.3.1 Two-State and Multistate Folders . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 6.3.2 Helix Dynamics .. . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 6.3.3 Hairpin Formation . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 6.4 Site-Specic Dynamics with Isotopic Editing . . . . .. . . . . . . . . . . . . . . . . . . . 6.4.1 Site-Specic Frequency Shifts . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 6.4.2 Insights into Folding Mechanisms on the Residue Level . . . . . 6.4.3 Single and Multiple Isotope Labels .. . . . . . .. . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 7 Light-Triggered Peptide Dynamics . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . Wolfgang Zinth and Josef Wachtveitl 7.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 7.2 Light-Triggered Peptides . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 7.2.1 The Photochromic Switching Unit . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 7.2.2 The Linking Group . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 7.2.3 The Peptide Moiety .. . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 7.3 Characterization of Light-Triggered Peptides by Stationary Spectroscopy .. . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 7.4 Methods for the Study of Ultrafast Structural Dynamics . . . . . . . . . . . . . 7.5 Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 7.5.1 Ultrafast Spectroscopy on Cyclic Azobenzene Peptides .. . . . . 7.5.2 Unfolding and Folding of a Light Switchable Hairpin Model Compound . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 7.5.3 Toward Light Switchable Tertiary Structures: (I) Azo-maquettes.. . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 7.5.4 Toward Light Switchable Tertiary Structures: (II) Azo-collagens . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 7.6 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 8 Time-Resolved FTIR Spectroscopy of pH-Induced Aggregation of Peptides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . John E.T. Corrie, Alex Per lvarez-Marn, and Andreas Barth a 8.1 Introduction to Infrared Difference Spectroscopy .. . . . . . . . . . . . . . . . . . . . 8.1.1 Principles .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 8.1.2 Triggering Protein Reactions .. . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 8.1.3 Interpreting Difference Spectra . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 8.2 Caged Compounds .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 8.2.1 Introduction to Caged Compounds . . . . . . . .. . . . . . . . . . . . . . . . . . . . 8.2.2 Caged Protons.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 8.2.3 Difference Spectrum of Caged Sulfate Photolysis . . . . . . . . . . . .

151 152 156 157 158 158 161 161 162 162 163 166 168 171 171 172 172 175 177 177 180 183 183 184 185 187 190 191 193 193 193 194 196 198 198 202 204

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8.3 Acidication-Induced Unfolding of Myoglobin .. .. . . . . . . . . . . . . . . . . . . . 8.4 Acidication-Induced Aggregation of the Alzheimers Peptide . . . . . . 8.4.1 Introduction to the Alzheimers Peptide . . .. . . . . . . . . . . . . . . . . . . . 8.4.2 Time-Resolved Infrared Difference Spectroscopy of the Aggregation of the Alzheimers Peptide .. . . . . . . . . . . . . . . 8.5 Outlook . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 9 Examining Amyloid Structure and Kinetics with 1D and 2D Infrared Spectroscopy and Isotope Labeling . . . . . . . . . . . . . . . . . . . . Lauren E. Buchanan, Emily B. Dunkelberger, and Martin T. Zanni 9.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 9.2 Vibrational Modes of Amyloids .. . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 9.3 Isotope Labeling Schemes .. . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 9.4 Vibrational Dynamics of Amyloids . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 9.5 Experimental Methods .. . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 9.6 Experimental Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 9.7 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . .

206 207 207 208 212 213 217

217 220 225 228 229 230 236 236

Index . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . 239

Contributors

A. Barth Stockholm University, Department of Biochemistry and Biophysics, Arrhenius Laboratories, 10691 Stockholm, Sweden, barth@dbb.su.se Joseph W. Brauner Rutgers University, Newark College, 73 Warren Street, Newark, NJ 07102, USA, matjoe63@verizon.net Lauren E. Buchanan Department of Chemistry, University of Wisconsin Madison, 1101 University Avenue, Madison, WI 53706, USA, lbuchanan@chem. wisc.edu John E.T. Corrie MRC National Institute for Medical Research, The Ridgeway Mill Hill, London NW7 1AA, UK, john.corrie@btinternet.com Emily B. Dunkelberger Department of Chemistry, University of Wisconsin Madison, 1101 University Avenue, Madison, WI 53706, USA, eblanco@chem.wisc. edu Heinz Fabian Robert Koch-Institute, Biomedical Spectroscopy, Nordufer 20, 13353 Berlin, Germany, FabianH@rki.de Karin Hauser Department of Chemistry, University of Konstanz, Universit tsstr. a 10, 78464 Konstanz, Germany, Karin.Hauser@uni-konstanz.de Tetsunari Kimura Institute for Molecular Science, 38 Nishigo-Naka, Myodaiji, Okazaki 444-8585, Japan, tkimura@ims.ac.jp Jonas Markgraf Faculty of Chemistry, Physical Chemistry I Biophysical Chemistry, TU Dortmund University, Otto Hahn Str. 6, 44227 Dortmund, Germany, jonasmarkgraf@gmx.de Richard Mendelsohn Rutgers University, Newark College, 73 Warren Street, Newark, NJ 07102, USA, mendelso@andromeda.rutgers.edu Gareth J. Morgan University of Leeds, Mount Preston Street, Leeds LS2 9JT, UK, garethjmorgan@gmail.com

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Contributors

Dieter Naumann Robert Koch-Institute, Biomedical Spectroscopy, Nordufer 20, 13353 Berlin, Germany, NaumannD@rki.de Alex Per lvarez-Marn Harvard University, 52 Oxford Street, NorthWest a Building, Cambridge, MA 02138, USA, peralvarezmarin@gmail.com Matthias Puhse Faculty of Chemistry, Physical Chemistry I Biophysical Chemistry, TU Dortmund University, Otto Hahn Str. 6, 44227 Dortmund, dr.matthias.puehse@googlemail.com Sheena E. Radford University of Leeds, Mount Preston Street, Leeds LS2 9JT, UK, s.e.radford@leeds.ac.uk Satoshi Takahashi Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Katahira 2-1-1, Aoba-ku, Sendai 980-8577, Japan, st@tagen.tohoku.ac.jp Josef Wachtveitl Institute of Physical and Theoretical Chemistry, GoetheUniversity Frankfurt/Main, Max von Laue-Strae 7, 60438 Frankfurt am Main, Germany, wveitl@theochem.uni-frankfurt.de Roland Winter Faculty of Chemistry, Physical Chemistry I Biophysical Chemistry, TU Dortmund University, Otto Hahn Str. 6, 44227 Dortmund, Germany, roland.winter@tu-dortmund.de Martin T. Zanni Department of Chemistry, University of Wisconsin Madison, 1101 University Avenue, Madison, WI 53706, USA, zanni@chem.wisc.edu Wolfgang Zinth Department of Biomolecular Optics, Faculty of Physics, LudwigMaximilians-University Munich, Oettingenstr. 67, 80538 Munich, Germany, wolfgang.zinth@physik.uni-muenchen.de