Unit I: What Makes a Cell (Chapters 1-3)

Introduction to Cells / The study of cells

Molecules of Life and Bioenergetics

Physiology in Focus: Metabolic Disorders

Proteins
 Chapter 3 Lecture Topics
Textbook Readings:
5th Edition: p. 125-187
6th Edition: p. 109-169

Protein Structure
Protein Function
Regulation of Protein Function
 Chapter 3 Questions/Objectives

I. What are the factors that determine the structure and

shape of proteins?

II. How is protein structure related to protein function?

III. What do proteins do?

a) binding

b) distinct functional classes:

Antibodies and Enzymes
 8 Common Features of All Cells

The actions of proteins underlie all of these features

1. Cells are highly complex and organized.

2. Cells possess a genetic program.
3. Cells are capable of producing more of themselves.

4. Cells are biochemical factories that constantly acquire and utilize energy.
5. Cells engage in mechanical activities.
6. Cells are able to respond to stimuli.
7. Cells are capable of self regulation.
8. Evolution first happens at the level of molecules and cells.
 Amino acid side chains have different chemical properties
No need to memorize any of these structures. You should be able to tell whether a given
side chain is nonpolar, polar or electrically charged, just by looking at it.
10 Amino acids you will need to know!
Know: Their 3-letter abbreviations and chemical properties
 (main chain)

Figure 3-1 Molecular Biology of the Cell ( Garland Science 2008)

Polypeptide chains often exist as
highly ordered, 3D structures.
Three major factors contribute to a proteins
structure:

Peptide backbone flexibility

Noncovalent attractions within polypeptide backbone

Noncovalent attractions between side chains (R groups)

 4 Levels of Protein Structure

primary secondary tertiary quaternary

Linear sequence Folding and Assembly of Assembly of

Of amino acids twisting of the multiple secondary multiple tertiary
within peptide structures structures
polypeptide backbone
chain
Driven by
Held together via hydrogen Driven by noncovalent R group interactions:
covalent bonding within (hydrogen bonding, electrostatic, hydrophobic)
(peptide) peptide
bonding backbone Can also be stabilized by a special type of
covalent bonding (disulfide bonds)
 Primary stucture
Leve1

Each amino acid in a polypeptide chain contributes

3 covalent bonds:

1. N-C flexible

2. C C

3. C N (peptide bond)
Inflexible; behave like double bonds
Two amino acids are unique in their covalent bonding properties
 Disulfide bonds can form between cysteine residues to
cross-link parts of a polypeptide backbone

These bonds can stabilize higher order (secondary and up) structures

Figure 3-28 Molecular Biology of the Cell ( Garland Science 2008)

12
Rigid proline residues insert a kink in a proteins
backbone and can disrupt higher order (secondary
and up) structures

13
 Secondary structure
Hydrogen bonding between amino group hydrogen atoms
Level 2 and carbonyl group oxygen atoms

Two types:
Alpha helix Rigid cylinder

Beta sheet
Flattened sheet
 Secondary structure: Helix

H-bonding occurs
between C=O and
N-H groups four
amino acids apart

Figure 3-7a,b,c Molecular Biology of the Cell ( Garland Science 2008)

 Secondary structure: sheet
H-bonding
occurs between
C=O and N-H
groups in
adjacent
polypeptide
chains

Figure 3-7d,e,f Molecular Biology of the Cell ( Garland Science 2008)

 Some proteins consist entirely of either only
alpha helices or only beta sheets

Fibroin (silk) Collagen (connective tissue)

Fibrous proteins consist of repeating units of one type of secondary structure

Such rigidity enables these proteins to provide structural support within cells
and tissues
 Tertiary Structure
noncovalent attractions among side chains (R groups)
Level 3

Unstructured loops (aka random coils) link secondary

and/or tertiary structures together
 Hydrophobic interactions among R groups drive protein folding

Figure 3-5 Molecular Biology of the Cell ( Garland Science 2008)

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 3D folding of
proteins results in structures that assume the
lowest possible energy state.

Unfolded state Folded state

GUNFOLDED GFOLDED

Protein stability depends on the free energy change between the folded and
unfolded states
G = GFOLDED - GUNFOLDED

A folded protein state is more stabilized than its unfolded state when:
GUNFOLDED > GFOLDED
 Quaternary structure
Level 4

Arrangement of multiple tertiary structures

Within the same protein
Between separate proteins
Quaternary structure of hemoglobin has 2 each of 2 subunits

Figure 3-22 Molecular Biology of the Cell ( Garland Science 2008)

 Interactions between R groups and the surrounding
environment can determine a proteins localization in the cell
Hydrophobic amino acids comprise alpha helices Polar amino acids comprise alpha helices

Bacteriorhodopsin = membrane protein Myoglobin = cytosolic protein

Figure 10-33a Molecular Biology of the Cell ( Garland Science 2008)

 Four different ways to depict protein structure
Example: The SH2 domain (panel 3-2)

Ribbon: enables visualizaiton of

Backbone: overall organization of
Secondary structures
Polypeptide chain

Wire: highlights the amino acid Space fill: contour map that shows
surfaces and pockets 23
side chains