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Chapter 4 How Can We Understand Structural

The Three-Dimensional Effects at the Molecular Level?

Structure of Proteins
• By determining the precise three dimensional
molecular structures of proteins
• In the presence and absence of their
substrates and prosthetic groups
• Starting with the folding constraints of the
polypeptide backbone itself…

Chapter 4 2

Overview of Protein Structure Overview of Protein Structure

Terms Protein structure can be broken down into four levels
• The spatial arrangement of atoms in a protein is called its conformation
Primary Structure:
– Possible conformations include any structural state that can be achieved the sequence of amino acids
Amino Acids
without breaking covalent bonds
– Changes in conformation are often associated with protein function
• Proteins in any of their functional, folded conformations are called native Secondary Structure:
α Helix Occurs when the sequence of amino
proteins β Sheet
structure is a
acids are linked with hydrogen bonds
• The stability of this conformation is largely governed by weak interactions vital key in
– A protein’s stability is its tendency to maintain a native conformation determining
β Sheet
Tertiary Structure: each protein’s
– Native proteins are only moderately stable with the ∆G separating folded Occurs when certain attractions are activity in
versus unfolded states in the range of 20 to 65 kJ/mol (under physiological present between alpha helices and
α Helix pleated sheets
• Most of the structural patterns found in folded proteins reflect two simple
rules: Quarternary Structure:
– Hydrophobic residues are want to be in the interior of the protein Is a protein consisting of more than
one amino acid chain
– The number of hydrogen bonds within the structure is maximized
Chapter 4 3

Protein Secondary Structure Overview of Protein Structure
Long chains of amino acids will commonly fold or curl Efforts of Linus Pauling & Robert Corey
into a regular repeating structure • Pauling, Corey and collaborators used X-ray diffraction to study the
structure of fibrous proteins (α-keratin and β-keratin)
– They identified two repeating patterns: (1) A 0.55 nm pattern in α-keratin and
(2) A 1.3 – 1.4 nm pattern in β-keratin
• Pauling also studied structures of small molecules containing amide
• From these studies, they proposed several principles that a protein
structure must obey:
– The bond lengths and bond angles should be distorted as little as possible
– No two atoms should approach one another more closely than is allowed by
their van der Waals radii
– The amide group must remain planar and in the trans configuration (this
allows for rotation only about the two bonds adjacent to the Cα)
– Some kind of non-covalent bonding is necessary to stabilize a regular folding
Chapter 4 5 Chapter 4 6

Overview of Protein Structure Overview of Protein Structure

Forces that Influence Protein Structure The Peptide Bond is Rigid and Planar
• Hydrogen Bonds: • The six atoms in the peptide group lie in a single plane, with the oxygen
– The atoms of the peptide bond will form hydrogen bonds whenever atom of the carbonyl group and the hydrogen atom of the amide nitrogen
possible trans to each other
– Amino side chains such as Arg, Asn, Gln, Lys and His reside on the
protein surface
• Hydrophobic Interactions:
– The interior of proteins contain hydrophobic residues almost
• Electrostatic Forces • The carbonyl oxygen has a partial negative charge and the amide
– Ionic Interaction: nitrogen a partial positive charge, setting up a small dipole
• The association between two groups of opposite charge is called a ion • This distribution of charge indicates that the C-N bonds are unable to
pair or salt bridge. rotate freely because of the partial double bond character
• However, these charged groups are usually solvated in aqueous solution
rather than free to from ion pairs • The N – Cα and the Cα – Cα are able to freely rotate
• Therefore, Ionic interactions do not contribute greatly to protein structure
or stability • Therefore the peptide backbone is like a series of rigid planes with
– Van der Waals: adjacent planes sharing a point of rotation at the Cα
• Induced electrical interactions that contribute significantly to the
Chapter 4 7 Chapter 4 8
conformational stability in the interior of the protein.

Overview of Protein Structure Overview of Protein Structure
The Peptide Bond is Rigid and Planar The Peptide Bond is Rigid and Planar
Conformation of the Peptide Backbone is Determined by • In principle, phi and psi can have any value between -180° and +180°
the Phi and Psi Rotational Bond Angles • However, there are many combinations of angles that are prohibited due
Φ (phi) is the N – Cα bond (hetero)
to steric interference between:
– atoms in the peptide backbone φ=0
– the AA side chains
• For the backbone: and
– is usually between –45° and –180°
– Psi is usually between –60° and +190°
is forbidden
– For proline, Phi is limited to –35° to –85°
• For the R Group:
Ψ (psi) is the Cα – C bond (hetero) – Think about the structure of the R Group The allowed values for phi and psi
are shown graphically when psi is
– Compare glycine and alanine plotted versus phi in a
• By convention, both phi and psi are defined as 180° when the polypeptide
is in its fully extended conformation and all groups are in the same plane Ramachandran Plot
Chapter 4 9 Chapter 4 10

Overview of Protein Structure Overview of Protein Structure

The Peptide Bond is Rigid and Planar The Peptide Bond is Rigid and Planar
A Ramachandran Plot for Polyglycine A Ramachandran Plot for Polyalanine
The Peptide Bond Alone Constrains “Conformational Space” A Methyl Group Further Constrains “Conformational Space”

Fully allowed
Fully allowed
At limits of
(not Val, Ile)
At limits of
allowability Allowed with
bond flexibility

Chapter 4 11 Chapter 4 12
Fig. 7-9 in Voet & Voet, 1990

Overview of Protein Structure Protein Secondary Structure
The Peptide Bond is Rigid and Planar
A Structurally Confined AA – Proline
• Protein Secondary Structure can be broken
into three main types:
– Helical Structure
Φ (phi) is limited – Sheet Structure
– Connective Structure
• These types vary in their size, hydrogen
bonding patterns and positioning of the R
Pro • In some cases, structure can select for or
against a particular Amino Acid R group.
Chapter 4 13 Chapter 4 14

Protein Secondary Structure Protein Secondary Structure

One Common Simple Structure is the β-Turn
• Compact protein folding requires frequent turns or loops, Whenever a bend is introduced…
where the backbone reverses direction
• Often used is the β-turn: The strands that enter and leave the bend
– A 4 AA loop, reversing direction by
must be antiparallel…
– Held together by an H-bond
between the C=O of AA1 and the
NH of AA4
– AA3 is often a Gly (always in Type
II) WHY?? In front Behind
– AA2 may be Pro WHY??
– The peptide linkage is flipped 180o in Type I vs Type II
– Structure usually occurs at surfaces, connecting anti-parallel β-sheets

Other Simple Secondary Structure includes:

Omega Loops
Chapter 4 15 Chapter 4 16
Disordered Regions

Protein Secondary Structure Protein Secondary Structure
Which may form a two-stranded secondary The β-Sheet
structure called a β-ribbon • β-sheets are composed of
extended polypeptide chains in
• In which hydrogen bonds form straight pleated sheets
across between the two strands, NH---O=C • The hydrogen bonds formed are
interstrand rather than
• Where adjacent pairs of AA sidechains intrastrand.
alternate projecting above and below the • The pleat is the result of the
tetrahedral nature of the Cα
plane of the β-ribbon followed by the planarity of the
peptide bond.
• Which has a slight right-hand twist • The R groups are perpendicular
• And which if continued, becomes a multi- to the peptide backbone sheet
and alternate (up and down) from
stranded antiparallel β-sheet face to face.
Molecular Biology of the Cell, Alberts et al., 2002
Chapter 4 17 Chapter 4 18

Protein Secondary Structure Protein Secondary Structure

Types of β-Pleated Sheets Antiparallel β-Sheet Top View
Parallel β-pleated
• H-bonds
sheets • R-groups
• Pleated character, most
• Both strands that are extended
involved in hydrogen • R1-R3 distance
bonding run in the same • β-bends connect
direction (both are N- to • Strands, avg. = 6
C- terminal). • Avg. strand length is
about 6 AA’s 0.7 nm
• The distance between
Side View
residues in the parallel Antiparallel
case is 0.325 nm, which is
Chapter 4 19 Chapter 4 20
shorter than in the

Protein Secondary Structure Protein Secondary Structure
Top View Parallel β-Sheet
• H-bonds distorted

R-group location
Pleated character

R1-R3 distance
Connected by RH Between
• Usually has more than 5

0.65 nm
• Avg. strand length is about
6 AA’s

Side View
Chapter 4 21 Chapter 4 22

Protein Secondary Structure Protein Secondary Structure

Helices Allow More Compact Structures than Sheets Possible Types of Helix
• H-bonds occur between C=O and H-N
• Helices exploit maximum H-bonding within strands,
using nearby groups (which ones?)
groups in r residues farther along the chain
ƒ 2.27 forbidden r=2
• One AA exception is proline (WHY?)
ƒ 310 rare r=3 long & thin
• The Helix may be either right or left handed
ƒ 3.613 common r=4 just right!
• An nm helix has: n residues/turn and m atoms
between the H-bonded ones
• A helix is also characterized by the number (n) of ƒ 4.416 rare r=5 short & fat
peptide units per helical turn and its pitch (p), (π-helix)
which is the distance the helix rises along its axis
per turn
Chapter 4 23 Chapter 4 24

The α-Helix
Protein Secondary Structure C-terminus

The α-helix Cα

• A helix is characterized by the number (n) of
peptide units per helical turn and its pitch (p),
which is the distance the helix rises along its
• Most common (about 25% of the amino Cα
axis per turn
• The alpha helix has a pitch of 5.4 Å and 3.6
acids in proteins are in this structure) 3.6 residues
residues per turn
5.4Å pitch Cα • There are 13 atoms along the backbone per
• Stability is greatly enhanced by internal van 13

turn. This standard helical conformation is
called a 3.613 helix
der Waals contacts

• The hydrogen bonds of the helix are arranged
Cα 10 so that the peptide carbonyl bond of the nth
12 9
• H-bonds are in-line, optimum distance 11 8 Cα residue points along the helix towards the
peptide N-H bond of the (n + 4)th residue
• R-groups project outward, and provide the 4
Cα 6
7 • The core of the alpha helix is tightly packed
with a diameter of about 6Å. This packing

main constraints on helical structure 2
3 allows the interior atoms to be in van der Waals
contact across the helix thereby maximizing
N-terminus 1
their association energies.

• Amino acid residues in an alpha helix have conformations with ψ = -60° and φ = - 45 to
- 50°. This combination of angles prevents steric repulsion from the R groups
Chapter 4 25 Chapter 4 26

Protein Secondary Structure Protein Secondary Structure

The α-Helical Wheel:
Ball and Stick – End View Handedness of α-Helix
3 • The α-helix has a handedness associated
with it, a direction of twist.
• All α-helices that are composed of L-amino
acids are right-handed helices.
• All α-helices that are composed of D-amino
acids are left-handed helices.
• Mixtures of D and L amino acids will not allow
6 α-helices to form.
• However, a left-handed helix is not normally
observed in nature because this twist causes
its R groups to come too closely into contact
2 9 8 with the peptide backbone
5 1

Chapter 4 27 Chapter 4 28

Protein Secondary Structure Protein Secondary Structure
R-Group Constraints on α-Helical Structure The Helix Dipole
• Each carbonyl of the helix is hydrogen
• Interactions between AA side bonded to the peptide amide proton four
chains can stabilize or destabilize residues farther up the chain.
a helical structure • All hydrogen bonds are parallel to the helix
– Proline is a “helix breaker” (WHY?) axis.
– Adjacent residues of like charge • All carbonyl oxygens point in one direction,
Asp while all of the amide protons point in the
prevent helix formation (by repulsion
and H-bond destabilization) opposite direction.
– High glycine content favors alternate • This gives the helix a macroscopic dipole
structures instead moment from the individual dipoles.

– Bulky residues destabilize sterically • Negatively charged species will frequently

bind near the N-terminus of an alpha helix
because of the positive dipole.
Chapter 4 29 Chapter 4 30

Protein Secondary Structure Protein Secondary Structure

Other Helicies A Large Fraction of Protein Structure is
The 310 Helix
α-Helix or β-Sheet
α-helix 310 helix π helix
• The 310 helix has a pitch of 6.0 Å and is
slightly thinner than the α-helix.
• Its torsion angles place it in a mildly
forbidden area of the Ramachandran
diagram and it is only observed in short
segments within proteins

The π Helix
• The π helix is a 4.416 helix.
• It has a mildly forbidden conformation and
has only been observed at the ends of a few
• It has a comparably wide and flat
conformation which is too small to admit
water molecules but too large for van der
Waals contacts of the interior atoms across
the helical axis.
Chapter 4 31 Chapter 4 32

Protein Secondary Structure Overview of Protein Structure
Ramachandran Revisited Amino Acid Sequence Determines 2° Structure of Proteins
A protein “knows” what its active conformation is!
Ramachandran Plot for
Pyruvate Kinase • Christian Anfinson conducted a denaturation
experiment to demonstrate this point.
• In 1957, he showed that ribonuclease A (124
AA’s), after having been completely denatured
using 8 M urea and 2-mercaptoethanol, regained
full enzymatic activity when the urea and 2-ME
were slowly removed by dialysis.
• Conclusion: the protein “knows” how to re-fold into
its active configuration.
Chapter 4 33 Chapter 4 34

Protein Secondary Structure Overview of Protein Structure

To summarize… A Serious Question:
• Each type of secondary structure (ribbon, sheet, helix, or How Can a Protein Become Compact?
bend) employs some amino acids preferentially over
• Each type of secondary structure is also determined by a Serum Albumin (585 aa’s)
characteristic range of phi and psi angles
• Secondary structural elements are connected by
“random coil” regions, whose structure is determined by
interactions with solvent and other parts of the protein
rather than by internal contacts
Secondary Structures such as α helicies, β
• The “conformational space” occupied by any given sheets and turns must be employed!
protein can be depicted on a Ramachandran plot
Chapter 4 35 Chapter 4 36

Protein Tertiary & Quarternary Structure Protein Tertiary & Quarternary Structure
3° Structure describes the folding of a protein’s 2° structure units together
Fibrous versus Globular Proteins
with the spatial dispositions of its side chains • Once we reach the 3° level, we can classify proteins into
This type of structure results from the interaction of two groups, fibrous or globular
the side chains and the peptide backbone
• Fibrous proteins have polypeptide chains arranged into
Possible interactions include: long strands or sheets
– Consist largely of a single type of 2° structure
Electrostatic Forces
Covalent bonding – Usually proteins that provide support and structure
Hydrophobic Forces • Globular proteins have polypeptide chains folded into
Non-covalent Interactions spherical or globular shapes
– Consists of several types of 2° structure
Proteins will select a
folding conformation that – Usually an enzyme or regulatory protein
gives the lowest free
Chapter 4 37 Chapter 4 38

Protein Tertiary & Quarternary Structure Protein Tertiary & Quarternary Structure
The Remarkable Fibrous Proteins Hair is Made of α-Keratin


In general, fibrous proteins are:

• built up from a single element of secondary structure How does a “Perm” work?

• insoluble in water (lots of hydrophobic residues) • The double coiled-coil amplifies the strength of the α-helix, like rope
• involved in structural roles within the cell • Hydrophobic R-groups (Ala, Val, Leu, Ile, Met, and Phe) interlock in a regular
pattern where the helices touch
• Covalent interchain disulfide links further stabilize keratins (rhinoceros horn is 18%
cysteine in S-S crosslinks)
Chapter 4 39 Chapter 4 40

Protein Tertiary & Quarternary Structure Protein Tertiary & Quarternary Structure
Some Helices Can Be Left-Handed! Connective Tissues are made of Collagen
• Proline is bad for right-handed helices, because of its φ / ψ angles and
its inability to form H-bonds (N is bonded to 3 carbons already)
• Left-hand single helix, 3 residues
per turn
• Polyproline, however, can form a left-handed helix with 3 residues per
turn, and a pitch of 9Å • 35% Gly, 11% Ala, 21% Pro / 4-
• Modified proline (4-hydroxyproline) allows the formation of hydrogen HydroxyP
bonds, and further stabilization of this unusual helical form
• Triplet Gly-X-Pro (or Gly-X-HyP)
• This post-translational modification requires vitamin C as a co-
substrate for 3 enzymes that are involved in the hydroxylation of both
proline and lysine • Supertwisted coiled coil is right-
handed, made of 3 left-handed α-
Why do we care?
Stronger than steel!
Chapter 4 41 Chapter 4 LH RH 42

Protein Tertiary & Quarternary Structure Protein Tertiary & Quarternary Structure
Collagen – End View of Triple Helix Collagen Fibrils Are Built From the Triple Superhelices
• The monomer is ~ 1000 AA
What effect would a • In the triplex, each may be
point mutation in a different in sequence
collagen monomer • Crosslinking of the triplexes (via
Gly unusual AA-links) gives more
have…? strength (but also more
brittleness, with age)
• Alignment is also tissue-specific,
and may vary in cartilage, bone
matrix, tooth dentin, skin,
tendon, and connective tissue
(e.g. lungs)

Ehlers-Danlos syndrome, for example! So, what is scurvy?

Chapter 4 43 Chapter 4 44

Protein Tertiary & Quarternary Structure Protein Tertiary & Quarternary Structure
Silk Fibroin: Antiparallel β-Sheet Stacking Globular Proteins are the Functional Workhorses of the Cell
• Functional variety reflects the variety of structural elements used to
• High tensile strength, construct them
but flexible – Includes Enzymes, Transporters, Motor proteins, Regulatory proteins,
• Mostly close-packed β- Immunoglobulins and Capsid proteins
• Because they are roughly spherical, there are lots of bends, loops,
sheets and folds
• Rich in Ala and Gly • These proteins are compact and comprise regions of α-helix, β-
(alternating – why?) sheets, β-turns, and others as well
• Protein stability results from “hydrophobic” core and disulfide bridges
• No covalent bonds • Structural motifs tend to be reused when similar functions are required
between strands or by the cell
sheets which gives the
material flexibility
Chapter 4 45 Chapter 4 46

Protein Tertiary & Quarternary Structure Protein Tertiary & Quarternary Structure
What General Principles Govern the Structures of One Nice, Simple, Globular Protein is Myoglobin
Globular Proteins? • A small protein (153 AA’s, 16.7 kD)
• Great stability is derived from internal hydrophobic • With a heme prosthetic group, so it can
interactions (very close packing allows van der • Bind oxygen in muscle cells
Waals forces to contribute strongly) • It is mostly α-helix (78% of its AA’s are in
• Polar groups are usually hydrated, and most are the 8 segments, from 7 to 23 AA’s long),
linked by turns (some of them β)
on the surface of the protein
• Much of its stability comes from
• Charged groups are likewise usually on the hydrophobic interactions
surface of the protein
• Peptide bonds are mostly trans, and Pro residues
are found at bends
• Smaller proteins often use disulfide linkages to
compensate for lower vol:surface area ratios
Chapter 4 47 Chapter 4 48

Protein Tertiary & Quarternary Structure Protein Tertiary & Quarternary Structure
Supersecondary Structures: All Alpha Supersecondary Structures: All Beta
β sandwich:
Helix-turn-Helix: Retinol Binding Protein
RNA-binding Protien Rop • Composed of two
• Two Helicies lie anti- separate sheets
parallel to one another and • Can be aligned or
are connected by a short orthogonal

β Barrel:
Globin Fold: Four Helix Bundle: Porin
Myoglobin Cytochrome b562 • Sheets wrap around
• Consists of 8 helicies • Helicies are part of a β Helix:
to form a complex
• The two at the end of single peptide chain Pectate Lyase
with a central core
the chain are anti- and connected to each • Excellent for trans- • New fold recently
parallel, forming a other by three loops discovered
membrane proteins
helix-turn-helix fold • Sheet wind around in
like porin
a helical structure
Chapter 4 49 Chapter 4 50

Protein Tertiary & Quarternary Structure Protein Tertiary & Quarternary Structure
Supersecondary Structures: Alpha / Beta Peptide Domains
Substrate Binding
Large Polypeptides (> 200 residues)
usually fold into two or more globular
clusters called Domains

These domains can have multiple

functions such as:

Substrate Binding
Segregation of Functions
α/β Horseshoe: Multi-functional Proteins
α/β Barrel:
Ribonuclease Inhibitor Domain Repeats
Phosphate Isomerase
• Does not form a barrel NAD-Binding
Spacer Domains
• Here, the sheets are Domain
because the sheet are
slanted nearly parallel D- glyceraldehyde-
nearly parallel to the
to the central axis due 3-phosphate dehydrogenase
central axis
to the twist of the
Chapter 4 51 Chapter 4 52

Protein Tertiary & Quarternary Structure Protein Tertiary & Quarternary Structure
Many proteins are not single peptide strands Symmetry in Oligomeric Structures
Instead, they are a combination of several distinct • Symmetry may be necessary to enhance function
peptide chains which function together as a unit
(can you think of examples…?)
• Types of symmetry include:
– Rotational (cyclic) – Cn
– Dihedral – Dn
– Helical

Chapter 4 53 Chapter 4 54
21-mer of Ferritin Single Subunit of Ferritin

Protein Tertiary & Quarternary Structure Protein Tertiary & Quarternary Structure
Rotational Superposition Multiple Symmetry Axes

All subunits can be related by rotation about one or both of two axis,
Subunits are related by rotation about q single n-fold axis, one of which is two-fold
where n is the number of subunits
Chapter 4 55 Chapter 4 56

Protein Tertiary & Quarternary Structure Protein Tertiary & Quarternary Structure
Larger Spherical Structures May Require More Helical Symmetry is “Open” and Long
Complex Symmetry Structures are Possible
Icosa = 20

Poliovirus capsid Tobacco Mosaic


Relation of all 20 triangular faces requires rotation about one or more

of three separate rotational axis
Chapter 4 57 Chapter 4 58

Protein Denaturation and Folding Protein Denaturation and Folding

The Protein Folding Problem The Weak Forces that Govern Protein
• Linear sequence (1° structure) determines three- Folding into 3o Structures
dimensional shape (3° and 4° structure) • Hydrogen bonds – 20 kJ/mole, but…
– They trade off readily with solvent (no net ∆G)
• Far too many possibilities for trial & error – They are highly directional
• There are many constraints (planar peptide bond, • Ionic interactions – 86 kJ/mole (vs. 20-40 in water)
proline, R-group interactions, etc.) in a low dielectric protein interior
– Fall off as the inverse cube of the distance
• And intermediate structures help – Are not directional
– structures involve nearby AA’s (except β-sheet)

• van der Waals – 9.3 kJ/mole (protein interior)
– 3° structures bring linearly distant AA’s together
• Interactions are stabilized by lots of weak forces • Hydrophobic interactions – 8 kJ/mole
– Nonpolar – minimize interactions with water
– Driven primarily by entropy
Chapter 4 59 Chapter 4 60

Protein Denaturation and Folding Protein Denaturation and Folding
The Thermodynamic “Free-Energy Funnel” of So in the folding of a protein…
Protein Folding
• There are two basic rules (after the secondary
structures are formed)
But in the cell, kinetics – Pack as close together as possible (why?)
may also contribute to – Minimize contacts between hydrophobic groups and
finding the correct water
• The average contribution to stability is only about
0.2-0.4 kJ/mole for each amino acid
– Totaling ~ 40 kJ/mole for a peptide of 100 AA’s (or only
about 2 hydrogen bonds…)
– So proteins are also rather susceptible to denaturation
Chapter 4 61 Chapter 4 62

Protein Denaturation and Folding Protein Denaturation and Folding

Reasons for Errors How Can You Measure “Unfolding”?
• Proteins may start to unfold due to
– Thermal challenge (high temperature)
– Chemical challenge (chaotropic agents – guanidine,
urea, soaps)
– pH (a protein is least soluble near its pI)
• Proteins may misfold due to
– Mutations that disrupt crucial contacts
– Degradation accompanying protein turnover
• Unfolding often results in insoluble aggregates • One characteristic is the Tm – temperature at
– Resulting from the exposure of previously buried which a protein is “half unfolded”…
hydrophobic residues
Chapter 4 63 Chapter 4 64

Protein Denaturation and Folding Protein Denaturation and Folding
Protein Renaturation Molecular Chaperones
• Molecular Chaperones are proteins that interact with partially folded or
• Many proteins can re-nature and
improperly folded polypeptides, facilitating correct folding
regain full function following mild • Heat Shock Protein 70 (Hsp70) and associated proteins
denaturation (what would – Bind unfolded regions to prevent aggregation
constitute harsh denaturation?) – Similarly facilitate folding during biosynthesis
• Disulfide linkages can re-form if – Block folding of some proteins prior to translocation to the correct
reducing agents are removed cellular compartment
• Chaperonins
• This phenomenon shows that
– Huge heptameric complexes (GroEL and GroES)
primary structure contains all the
– Required for folding of 10-15% of E. coli proteins
information necessary to
• Protein disulfide isomerase (PDI) and peptide prolyl cis-trans
reconstitute 2o, 3o, and 4o isomerase
structures – Shuffle disulfide cross-links to the correct conformation
– Interconvert proline peptide bonds that hinder folding
Chapter 4 65 Chapter 4 66

Protein Denaturation and Folding Protein Denaturation and Folding

Some Chaperones are Heat Shock Proteins Chaperonins: Facilitated Folding
• These “hsp’s” are
induced by a rapid
• They can counter
the potentially
deleterious effects
of cellular “heating”
(namely ?) • In E. coli, ~ 15% of proteins need help from the GroEL/ES
complex to fold correctly
• And provide a • This ATP-dependent event occurs in an internal
kinetic “buffer” to sequestered pocket of the double heptamer
Chapter 4 the process 67 Chapter 4 68