Transcript Protein Structure and Function

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I am Hyun-Soo Cho, in Biology Department.
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Protein Structure and Function
CHAPTER1.
From Sequence to Structure
1-0. Overview
: Protein Function and Architecture
Figure 1-1. Four examples of biochemical functions performed by proteins
1-0. Overview
: Protein Function and Architecture
Figure 1-1. Four examples of biochemical functions performed by proteins
1-0. Overview
: Protein Function and Architecture
Figure 1-1. Four examples of biochemical functions performed by proteins
1-0. Overview
: Protein Function and Architecture
Sheet & strand
Figure 1-1. Four examples of biochemical functions performed by proteins
1-0. Overview
: Protein Function and Architecture
Figure 1-2. Levels of protein structure illustrated by the catabolite activator protein
1-1. Amino Acids
Figure 1-3. Amino-acid structure and the chemical characters of the amino-acid side chains
Structure and Stereoisomerism of a-Amino Acids
Ca : a-carbon (chiral) NH3+ : amino group COO- : carboxyl group R : functional group
(side chain)
Absolute Configuration : S
Absolute Configuration : R
Left, Counter-Clockwise
Right, Clockwise
Only L-amino acids
are constituents of
proteins.
1-1. Amino Acids
Figure 1-3. Amino-acid structure and the chemical characters of the amino-acid side chains
1-1. Amino Acids
Figure 1-3. Amino-acid structure and the chemical characters of the amino-acid side chains
The amino-acid side chains have different
tendencies to participate in interactions

Hydrophobic residues: van der Waals interactions – tendency to
avoid contact with water and pack against each other 
hydrophobic effect
- Ala & Leu are strong helix-favoring residues, Proline are not
because its backbone nitrogen isn’t available for H-bond
- Aromatic side chain of Phe participates in weakly polar interactions

Hydrophilic residues : Hydrogen bonds to one another, to peptide
backbone, to polar organic molecules, and to water.
- pKa shift: Asp & Glu (57 in hydrophobic interior or nearby (-)
charge), Lys (106 in ?)
- His: most versatile, most often found in enzyme active sites, pKa is
6, neutral, proton donator and acceptor
- Arg: completely protonated at neural, compared to Lys?
- Cys: common in enzyme active site, most powerful nucleophile.
Compared to Ser?

Amphipatic residues : both polar and nonpolar character
- Lys: hydrophic charged region, long hydrophobic region
(methylene) involved in van der Waals interactions with
hydrophobic side chains
- Tyr: pKa is 9, in some enzyme active site, hydroxyl group can be
donor and acceptor of H-bond. Aromatic ring can form weakly polar
interactions
- Trp: similar to Tyr, indole amide hydrogen don’t ionize.
- Met: least polar among amphipatic residues, thioether sulfur is
excellent ligand for metal ions.
van der waals interaction
- caused by transient dipoles, the momentary random fluctuation
in the distribution of the electrons of any atoms
Hydrophobic Effects?
1-2. Genes and Proteins
The genetic code is degenerate
Figure 1-4. The genetic code
1-2. Genes and Proteins
Splicing
And ?
Figure 1-5. The flow of genetic information in prokaryotes (left) and eukaryotes (right)


Alternative splicing can lead to truncated proteins,
proteins with different stretches in the middle, and
frameshifts.
Coding sequences can also be modified by RNA editing;
some nucleotides can be changed and additional
nucleotides inserted into the mRNA sequence before
translation.
Genetic code organization

Single-base changes (single-nucleotide polymorphism)
in the third position in a codon produce the same amino
acid. Changes elsewhere in the codon produce a different
amino acid, but with the same physical-chemical propherties.
The second base specifies if the amino acid is polar or
hydrophobic.  Conservative substitutions.
1-2. Genes and Proteins
Figure 1-6. Table of the frequency with which one amino acid is replaced by others
in amino-acid sequences of the same protein from different organisms
1-3. The Peptide Bond
Figure 1-7. Peptide bond formation and hydrolysis
1-3. The Peptide Bond
Resonance of peptide bond
- Polarity, Dipole moment
- partial double-bond character
Figure 1-8. Schematic diagram of an extended polypeptide chain
1-3. The Peptide Bond
Ramachandran plot
Figure 1-9. Extended polypeptide chain showing the typical backbone bond lengths and angles
1-4. Bonds that Stabilize Folded Proteins
Folded proteins are stabilized mainly by weak noncovalent interactions
1 kcal = 4.2 kJ
Figure 1-10 Table of the typical chemical interactions that stabilize polypeptides
1-5. Importance and Determinants
of Secondary Structure
Peptide back bone C=O and N-H tend to hydrogen bond with one another,
which result in the secondary structure. Especially in the interior of proteins.
Figure 1-11. Ramachandran plot
Rotational Properties of Peptide Bonds
Peptide bonds are rigid…
But,
the bonds containing the a-carbon between two peptide
bonds
can be rotated from -180o to +180o.
 : the angle of rotation about the bond between the nitrogen and the a-carbon
y : the angle of rotation about the a-carbon and the carbonyl carbon
1-5. Importance and Determinants
of Secondary Structure
Prediction of secondary structure elements from a. a sequence is accurate
to only about 70%.  convenient way of fold classification
N+3
N
Figure 1-12.Typical beta turn
beta turn, reverse turn, hairpin turn
1-6. Properties of the Alpha Helix
N
N+4
Figure 1-13.The alpha helix
1-6. Properties of the Alpha Helix
 Lipid bilayer thickness? 30A. To span the cell membrane, how long helix?
at least 20 residues long helix
 All helices in real protein structures are right-handed. Why?
because of steric hindrance caused by L-configuration
 Helix dipole increase with increasing length of the helix
At the N-terminal ends of helices  negative side chain
Figure 1-14.Table of helical parameters
1-6. Properties of the Alpha Helix
Alpha helices can be amphipathic, with one polar and one nonpolar face
Figure 1-15.View along the axis of an idealized alpha-helical polypeptide
1-6. Properties of the Alpha Helix
1) Special examples of a-helix
Collagen : bone, tendon, ligament and blood vessel
Every third residue, glycine (GlyXY)n, X & Y proline
-Proline lacks N-H groups,
 hydroxylation!
Figure 1-16.The structure of collagen
• Collagen: the most abundant protein of mammals, main fibrous
component of skin, bone, tendon, cartilage, and teeth. (피부미용)
2) Special examples of a-helix
Coiled-coil protein
• Structural support for Cells and Tissues
 a-keratin: left-handed superhelix of two right-handed a helices.
from wool & hair, intermediate filaments in cytoskeleton,
muscle protein (myosin & tropomyosin)
 Heptad repeats; Every seventh residue in each helix, Leu holds
two helix by van der Waals interactions
 disulfide bond crosslinks: fewer – flexible, more – harder (horns,
claws etc)
1-7. Properties of the Beta Sheet
Figure 1-17.The structure of the beta sheet
1-7. Properties of the Beta Sheet
No Plain b-sheet
Only twisted b-sheet.
Why?
Stability & integrity
of b-sheet depends on # of b-strands
Figure 1-18. Two proteins that form a complex through hydrogen bonding
between beta strands (the Rap-Raf complex, PDB 1gua)
1-7. Properties of the Beta Sheet
b strands usually have a pronouced
right-handed twist, due to steric effects
arising from the L-amino acid configuration.
Figure 1-19. Beta barrel ; closed cylinder, retinol-binding protein
1-8. Prediction of Secondary Structure
A-helices prediction
Is easier than b-sheet
Figure 1-20.Table of conformational preferences of the amino acids
1-8. Prediction of Secondary Structure
Figure 1-21. An example of secondary structure prediction
1-9. Folding
The structure of a protein is directly determined by its primary structure
Figure 1-22. Folding intermediates
1-9. Folding
Competition between self-interactions and interactions with water drives
Protein folding
Figure 1-23. Highly simplified schematic representation of the folding
of a polypeptide chain in water
Computational prediction of folding is not yet
reliable

Ab initio method
- Equilibrium conformation is the global free-energy minimum
- potential energy parameter is accurate (H-bond, van der Waals etc)
- key intermediates?
- oligomerization can not be addressed although very many globular
proteins are oligomeric.
Protein folding funnel
The hydrophobic environment of a membrane permits
only all-helical and all-beta-barrel integral membrane
•
The polar amide and carbonyl group should hydrogen bond to
one another because water can’t involve in H-bonds
1-10. Tertiary Structure
The condensation of multiple secondary structural elements leads to
tertiary structure
•Two proteins with similar secondary structure elements but different tertiary
structures
Figure 1-24. Comparison of the structures of triosephosphate isomerase and dihydrofolate reductase
1-10. Tertiary Structure - loops
Found at the surface of protein and
Exposed to the solvent
Sites for protein recognition, ligand
Binding and membrane interaction
Often mutation sites without
changing the core structure
Often move as rigid bodies because
their side chain pack together
Figure 1-25.Variable loops
1-10. Tertiary Structure
• Protein crystals contain more than 50% waters in their volumn
• hydration shell
• a few water inside the protein makes important interactions as
part of the tertiary structure
Figure 1-26. Porcine pancreatic elastase showing the first hydration shell surrounding the protein
1-10. Tertiary Structure
The atoms are packed as closely as in a
solid. A few cavities and small channels
provide some flexibility.
Packing by ionic bonds, H-bonds, and
van der Waal interactions.
Packing types
Figure 1-27. Cut-away view of the interior of a folded protein
1-10. Tertiary Structure
The protruding side chains of one helix fit into grooves along the surface
of the other helix: ridges and grooves
Figure 1-28. Packing motifs of a helical structure
1-11. Membrane Protein Structure
H-bond in a completely nonpolar environment
are considered stronger than in water
Figure 1-29. A segment of a simulated membrane bilayer
1-11. Membrane Protein Structure
a helices are the most common secondary structure in membrane proteins
Hydrophobic
side chain
Polar side chains
interacting with polar
head group of the lipids
and each other
Figure 1-30. The three-dimensional structure of part of the cytochrome bc1 complex
1-11. Membrane Protein Structure
Average hydrophobicity of an eight-residue along the sequence
: hydrophathy
Prediction of membrane a helices
; 20 consecutive hydrophobic residues
Figure 1-31. Hydropathy plot of the Rhizobium meliloti protein DctB
1-11. Membrane Protein Structure
• Membrane b sheet prediction is difficult
because of various b strands tilt (above 8-9 a.a)
• all sheet are antiparallel sheet with short polar turns
• all b barrel: hydrophobic side chains in surface,
polar side chain inside of the barrel
common in channel
How about a mixed structure of
b sheet and a helix?
Figure 1-32. The three-dimensional structure of the all-beta transport protein FhuA
1-11. Membrane Protein Structure
•View looking down the channel
•The pore-forming loop, 2 K+ ions
• Nobel prize in chemistyr 2003
- Roderick Mackinnon (kcsA K+ channel)
- Peter Agre (water channel)
Figure 1-33.Three-dimensional structure of the bacterial potassium channel
The Nobel Prize in Chemistry 2003
"for structural and mechanistic studies of ion channels"
Roderick Mackinnon succeeded in
determining the first high-resolution
structure of an ion channel, the kcsA
K+ channel from streptomyces lividans.
Water channel and ion channel
13.6 Specific channels increase the permeability of
some membranes to water
-Some tissues need to transport water.
-kidney, secretion of saliva and tears.
※ Aquaporin (Peter Agre in red-blood-cell membrane)
-Water channel. 24kda membrane protein
-6 membrane spanning helices.
-Positive residues in the center prevent the transport of protons through
aquaporin; maintain proton gradients
Ion channel
Potassium and sodium ion
For the potassium ions the
distance to the oxygen atoms
in the ion filter is the same as
in water.
The sodium ions, which are
smaller, do not fit in between
the oxygen atoms in the filter.
This prevents them from
entering the channel.

The atomic radius K+ is 1.33 Å and that of Na+ is 0.95 Å .
The different kinds of K+ channels gating (opening)
• ligand gated
- dependent on the intracellular Ca2+ concentration
- the level of certain G-protein subunits in the cell
- cytoplasmic or extracellular domains for binding ligands.
• voltage gated
- the membrane voltage-dependent.
- integral membrane domains for sensing voltage differences.
The Structure of the Potassium Channel
four usually identical subunits that encircle with four-fold symmetry
→ inner, outer, pore α -helix
Molecular surface of KcsA and contour of the pore
the entire internal pore
The ion conduction pore of K+ channels
a pore helix (red) and a selectivity filter (gold). Blue mesh shows
electron density for K+ ions and water along the pore.
The ion conduction pore of K+ channels
Selective ion conduction
K+ channels conduct K+ ions specifically because the
selectivity filter contains multiple binding sites that mimic
a hydrated K+ ion’s hydration shell. Potassium channels
achieve high conduction rates by exploiting electrostatic
repulsion between closely spaced ions and by coupling the
conformation of the selectivity filter to ion binding within the
filter.
1-12. Protein Stability
: Weak Interactions and Flexibility
The folded protein is a thermodynamic compromise
•Stability is a net loss of free energy (entropy + enthalpy)
Free energy difference between the folded and unfolded states;
~21-42kJ/mole, marginally stable.
•Folding decrease the entropy of the proteins
; but increase of water entropy is much bigger
(hydrophobic effect)
Water’s role in weak interactions
1. Small enthalpy difference.
2. Hydrophobic effect – entrophy
(nonpolar groups in water tend to be
Surrounded by a cluster of water mols)
Figure 1-34. Illustration of the ordered arrays of water molecules surrounding exposed
hydrophobic residues in bovine pancreatic ribonuclease A
1-12. Protein Stability
: Weak Interactions and Flexibility
Protein structure can be disrupted by a variety of agents
• CD shows protein conformation.
• Denaturants (urea, guanidinium
hydrochloride, SDS) competes for
H-bonds with polar groups of the
back bone and side chains.
• Features of themophilic proteins
- more salt bridges
- more hydrophobic interactions &
shorter loops
Figure 1-35. Computed circular dichroism spectra for the evaluation of protein conformation
1-12. Protein Stability
: Weak Interactions and Flexibility
The marginal stability of protein tertiary structure allows
proteins to be flexible
All chemical bonds are flexible because of
Vibration and rotation
Proteins are much more flexible because of
weak interactions to break and reform frequently
– Thermal fluctuation is essential for protein
function (up to a few angstroms)
- Adjust to the binding of ligand or substrate
- Water penetration into the interior of the
protein
Figure 1-36. Results of a molecular dynamics simulation of two interacting alpha helices
1-13. Protein Stability
: Post-Translational Modifications
Covalent bonds can add stability to tertiary structure
1.Disulfide bond between cysteine side chains
-Oxidation of two sulfhydryl groups in ER
- not found in most intracellular proteins,
but common in secreted proteins
Figure 1-37. The structure of the small protein bovine pancreatic trypsin inhibitor, BPTI
1-13. Protein Stability
: Post-Translational Modifications
2. Coordinate covalent bonds
-Coordination of a metal ion to side chains or water molecules
- Ca2+ , Zn2+ most common
-removal of the metal ions can leads to denaturation (EDTA)
Figure 1-38. Stabilization by coordinate covalent bonds
1-13. Protein Stability
: Post-Translational Modifications
3.Organic or organometallic cofactor at the active site
Pyridoxal phosphate in D-amino
acid aminotransferase
Methionine S and heme iron in Cytochrome C
Porphyrin cofactor - covalent bonds
Heme iron in myoglobin
PQQ in polyamine oxidases
Figure 1-39. Examples of stabilization by cofactor binding
1-13. Protein Stability
: Post-Translational Modifications
Glycosylation at serine, threonine or asparagine residues
-N-glycosylation site : NxS/T motif
-Most important for protein stability, folding, protein-protein recognition
(blood cell surface proteins, prevent cells from sticking to one another, cell walls)
-Deglycosylation can lead to unfolding or to aggregation. Stability change!
-Generally not alter the tertiary structure of a protein, Crystal Structure?
Phosphorylation and N-acetylation are
reversible and conformational switches
Histones or DNA methylases &
Demethylases (JMJD2A, LSD1)
Histone acetylation & deacetylation
(CBP, HDACs)
Figure 1-40.Table of post-translation modifications affecting protein stability
Each histone is organized
in two domains, a characteristic ‘histone fold’ and an unstructured
N-terminal ‘tail’. The histone-fold domains constrain the
DNA in a central core particle and, thereby, restrict access of
DNA-binding proteins.
This histone tail is a flexible amino terminus of 11-37 residues.
Several positively charged lysine side chains in the histone tail may
Interact with linker DNA, and the tails of one nucleosome likely interact with
Neighboring nucleosomes  higher-order coiling.
The histone tail lysine, especially those in H3 and H4, undergo reversible
acetylation and deacetylation by enzymes such as CBP (P300) and HDACs
In the acetylated form, the positve charge of the lysine e-amino group is
neuralized. This eliminate its interaction with a DNA phosphate group.
So the greater the acetylation of histone N-terminus, the less likely chromatin
is to form condensed 30-nm fibers and possibly higher-order folded
structures.
Sites of Histone Tail Modifications
Epigenetics edited by Allis et al. (2007)
1-14. The Protein Domain
Globular proteins are composed of structural domains
-Domain is a structural and functional unit composed of generally continuous amino
acids (50~200 a.a.)
-Domains have hydrophobic cores
Tetramerization and DNA-binding domain
Lac repressor tetramer binding to DNA
Interuption!
Alanine racemase
1-14. The Protein Domain
Multidomain proteins probably evolved by the fusion of genes that once
coded for separate proteins
-A single gene is assumed to have been duplicated in tandem
-The more ancient the gene duplication, the more time for mutation to happen
- examples
Two subunits
Figure 1-43. Structures of thioesterase and thioester dehydrase
1-14. The Protein Domain
Gene duplication within a single structural domain
Two nearly identical domains
Figure 1-44. Structure of gamma-crystallin, eye-lens protein
1-14. The Protein Domain
The number of protein folds is large but limited
- Protein folds are used repeatedly in different combinations
Figure 1-45. Structures of tryptophan synthase and galactonate dehydratase
1-15. The Universe of Protein Structures
Proteins are grouped into families on the basis of the domains, whose
functions are classified.  Tempting but not the all case.
Kinases, a/b hydrolase
SH2: phospho-tyr, SH3: proline-rich
PH: bind to membrane
Figure 1-46. Schematic diagram of the domain arrangement
of number of signal transduction proteins
1-15. The Universe of Protein Structures
Common TIM barrel of eight-stranded parallel beta barrel
But different biochemical functions; exceptional case!
-use NADPH to reduce sugars.
-hydrolyze phosphate goups
Figure 1-47. Structures of aldose reductase (left) and phosphotriesterase (right)
Both enzymes catalyze the same reaction but they have no structural
Similarity to each other in a.a. sequence and tertiary structure
Figure 1-48. Structures of aspartate aminotransferase (left) and
D-amino acid aminotransferase (right)
The modular structure of protein structure
allows for sequence insertions and deletions
Q: How long polypeptides domains can be inserted in or deleted from

a protein structure without disrupting structure?
Q: Insertions and deletions nearly always occur in the surface loop. Why?
1-16. Protein Motifs may be defined by their
primary sequence or by the arrangement of 2nd
structure elements
Protein Motif
• sequence motif/structural motif
• functional motif
Zinc finger motif – sequence motif
CXX(XX)CXXXXXXXXXXXXHXXXH
Figure 1-49. Zinc finger motif
1-16. Protein Motifs
• Functional motif
• Structural motif
Human growth hormone
Figure 50. Helix-turn-helix
Four-helix bundle motif
1-16. Protein Motifs
•Identifying motifs from sequence is not straightforward.
•Functional motifs are detected from the structure rather than the sequence.
Figure 1-52. Catalytic triad of serine protease (a) subtilisin, (b) chymotrypsin.
1-17. Alpha Domains and Beta Domains
Group domain folds into 5 classes, based on the predominant
secondary structure.
•Alpha domains:
•Beta domains: only beta sheet
•Alpha/beta domains: beta strands with connecting helical
segments
•Alpha+beta domains: separate beta sheet and helical regions
•Cross-linked domains: secondary structure are stabilized by
disulfide bonds or metal ions
1-17. Two common motifs for alpha domains
Four-helix bundle
- Common in hormones
Oxygen-strage protein in marine worms
4 helices, 20 degree tilt,
Myohemerthrin
Globin fold
Oxygen-strage protein
8 helices, 90 and 50 degree tilt
Hydrophobic pocket for organometalic
Myoglobin
1-17. beta domains contain strands
connected in two distinct ways
1. Connected to adjacent strand;
Up-and-down structural motif
Neuraminidase beta-propeller domain
2. Connected to 3rd strand;
Greek key motif
Pre-albumin
1-17. Antiparallel beta sheets can form
barrels and sandwiches
All-beta domains contain antiparallel beta strcuture, the strands
of which are connected with beta turns and larger loops
Beta sandwiches
-Antiparallel beta sheets pack against each other;
one face of b sheet orients to solvent, and
the other face orient toward the hydrophoic core.
-two greek-key motifs
Figure 1-56. Immunoglobulin
1-17. Beta Domains; variation
Jelly roll: variation of beta sandwich Fibrous protein silk: two-sheet structure
Sequence: GAGSGAGSGAGSG
Figure 1-59. Bacteriochlorophyll A protein
1-18. Alpha/Beta, Alpha+Beta
and Cross-Linked Domains
In alpha/beta domains, each strand of parallel beta sheet is usually connected
to the next by an alpha helix giving rise to beta-alpha-beta-alpha units
Right-handed crossover connection
Right-handed twist of the beta sheet
prefered the right-handed crossover topology
left-handed crossover connection
Figure 1-60. Crossover connection between parallel beta strands
1-18. Alpha/Beta Domains
Two major families of a/b domains: a/b barrel and a/b twist
•a/b barrel, TIM barrel Triosphosphate isomerase
•Parallel & Nonpolar beta strand followed by a
amphipathic Alpha helix, repeated eight times
Figure 1-61. Alpha/beta domains
•a/b twist,
Semi-aldehyde dehydrogenase
parallel b strands protected from
water by a helices coating
Nucleotide-binding fold
1-18. Alpha+Beta Domains
Alpha+beta domains have independent helical motifs packed against
beta sheet; segregated!
MHC
Figure 1-62. Alpha+beta saddle,TATA-binding protein
1-18. Cross-Linked Domains
In small irregular domains, disulfide bridges and metal ions form cross-links
Scorpion toxin
-Very stable to proteolytic
Digestion and heat denaturation
-No hydrophobic core but stabilized
by 4 disulfide bonds
Figure 1-63. Disulfide-linked protein
1-18. Cross-Linked Domains
2 histidines and 2 cysteines
Coordinate a zinc ion.
Too small to have hydrophobic core
The most abundant one in the human
Figure 1-64. Zinc finger
1-19. Quaternary Structure
: General Principles
Oligomers: composed of more than one polypeptide chain
subunits
Hemoglobin
Most common
Figure 1-65. Schematic representations of different kinds of oligomers
1-19. All specific intermolecular interactions
depend on complementarity
Protein surface is irregular.
What doest enable proteins to bind specific molecules?
Shape complementarity is necessary for large number of weak interactions
and to maximize the strength of interactions ((H-bonds and van der Waals)
Figure 1-66. “Open-book” view of the complementary structural surfaces that form the interface
between interleukin-4 (left) and its receptor (right)
1-19. Shape complementarity
For stable complex,
Bond strength should be greater
than about 15-20 kJ/mole.
So shape complementarity is
necessary.
tropomyosin
Figure 1-67. Coiled-coil alpha-helical interactions
1-19. Shape complementarity
C
C
Heptad repeat
Transcription factors of leucine zipper
On monomers are disordered
But fold on dimerization by hydrophobic
Interactions
N
N
Figure 1-68. Peptide-peptide interactions in the coiled coil
of the leucine zipper family of DNA-binding proteins
1-20. Quaternary Structure
: Intermolecular Interfaces
Formation of intermolecular interface
Is mediated by hydrophobic interactions,
Hydrogen bonds and salt briges
Including metal-ion ligation and disulfide bond
Hemoglobin: several intersubunit salt bridges
Depending on pH, alter the relative orientation
of the subunits & the affinity for oxygens
Very stable oligomers tend to bury a large
hydrophobic surface area between subunits
while polar interactions more easily break
Figure 1-69. Water molecules at a subunit interface
1-20. Quaternary Structure
: Intermolecular Interfaces
Rap
Raf
Figure 1-70. Oligomerization by beta sheet formation
1-20. Inappropriate quaternary interactions
induce disease
Hydrophobic patch from the mutation in b2 subunit (Gln  Val)
Thick fiber
Figure 1-71. Sickle-cell hemoglobin
1-20. Quaternary Structure
: Intermolecular Interfaces
Oligomeric proteins are more susceptible to disruption by mutation
Monomeric proteins; loss of function occurs in homozygous conditions
Oligomeric proteins: loss of function may occur in heterozygous conditions
Why oligomer in terms of evolution?
Figure 1-72. Dominant-negative phenotype resulting from hydrophobic interactions
between mutant and normal subunits of a dimeric protein
1-21. Protein assemblies built of identical subunits
are usually symmetric
Asymmetric complex
Figure 1-73.The human growth hormone-receptor complex
1-21. Protein assemblies built of identical
subunits are usually symmetric
Asymmetric unit is
Protomer.
Figure 1-75. Interactions underlying different geometric arrangements of subunits
1-21. Quaternary Structure: Geometry
Figure 1-74. Examples of quaternary arrangements observed for oligomeric proteins
1-21. Quaternary Structure: Geometry
rhinovirus
proteasome
Figure 1-74. Examples of quaternary arrangements observed for oligomeric proteins
1-22. Proteins are flexible
Figure 1-76.Table of protein motions
1-22. Conformational fluctuations in domain
structure tend to be local
Common ligand-induced
conformational change is the
lid-like movement of a
polypeptide segment to cover
a ligand-binding site.
Figure 1-77.Triosephosphate isomerase
1-22. Protein Flexibility
Alternate between distinct conformations
Free-energy barrier
Figure 1-79.T4 lysozyme
1-22. Protein Flexibility
Driving force is provided by ligand-protein
Interactions
Induced fit
Figure 1-80. Aspartate aminotransferase, open and closed forms