Transcript Chapter 3 - Proteins

Chapter 3 - Proteins
Test Your Knowledge About Basic Protein Structure
• Name one polar and one nonpolar amino acid, then make a list of
all the additional amino acids that you remember.
• What are the four weak (noncovalent) interactions that
determine the conformation of a protein?
• (True/False) A protein is at a near entropy minimum (point of
lowest disorder, or greatest order) when it is completely
stretched out like a string and when it is properly folded up.
Explain.
• (True/False) Loops of polypeptide that protrude from the
surface of a protein often form the binding sites for other
molecules. Explain.
• (True/False) For a family of related genes that do not match
genes of known function in the sequence database, it should be
possible to deduce their function using “evolutionary tracing” to
see where conserved amino acids cluster on their surfaces.
Explain.
Also Pro, Phe, Met, Trp, Gly, Cys
Reactions that promote protein folding
Adapted from L. Wu et al., 1995, Nature Struc. Biol. 2:281; courtesy of J. Harris and P. S. Kim
Molecular chaperones
Chaperones
Video – chaperone-aided protein folding
• Average length ≈ 10 residues ≈ 15 Å.
• Minimum length = 4 residues: how many H-bonds?
• Maximum length = 40 residues.
• Pleated - look edge-on
• Strands ~ 5 Å apart
• Note direction of H-bonds will differ in antiparallel & mixed sheets
Loops & Turns
•Connect secondary structural elements.
•Loops often carry the functional groups.
•Hairpin turns: Shortest possible loops
(2 residues).
•Gly often in tight turns.
Motifs (protein folds)
Beta-Hairpins I
Beta-Hairpins II
Beta Corners
Beta Barrels
Helix Hairpins
Alpha-Alpha Corners
E-F Hand
Helix-Turn-Helix
Beta-Alpha-Beta Motifs
Greek Key Motifs
Domains/Modules
Pyruvate kinase
• B sheet core with protruding loops
• Loops for binding interactions
• N and C terminals at opposite poles or
form “plug-ins”
Domain shuffling
Families/Clans
Pyruvate kinase
This is a member of the Pyruvatekinase-likeTIM barrel superfamily
Other families
GP120
Family
Envelope glycoprotein GP120
RVT_1
Family
Reverse transcriptase (RNA-dependent DNA polymerase)
COX1
Family
Cytochrome C and Quinol oxidase polypeptide I
Oxidored_q1
Family
NADH-Ubiquinone/plastoquinone (complex I), various chains
MFS_1
Family
Major Facilitator Superfamily
HCV_NS1
Family
Hepatitis C virus non-structural protein E2/NS1
Serine Protease family
Other Important Protein
Structural Features
• Subunits
– Dimers, tetramers, large
assemblies of monomers
• Filamentous proteins
• Globular proteins
Video – clathrin assembly
Table 1.
Proportions of
amino acids
that are
inaccessible to
solvent in a
study of
twelve
proteins.
Amino
Acid Side
Chain
Proportion
Buried
I = Ile
0.60
V=Val
0.54
C=Cys
0.50
F=Phe
0.50
L=Leu
0.45
M=Met
0.40
A=Ala
0.38
G=Gly
0.36
W=Trp
0.27
T=Thr
0.23
S=Ser
0.22
E=Glu
0.18
P=Pro
0.18
H=His
0.17
D=Asp
0.15
Y=Tyr
0.15
N=Asn
0.12
Q=Gln
0.07
K=Lys
0.03
R=Arg
0.01
Test Your Knowledge Now
Small proteins may have only one or
two amino acid side chains that are
totally inaccessible to solvent. Even in
large proteins, only about 15% of the
amino acids are fully buried. A list of
buried side chains from a study of
twelve proteins is shown in Table 1.
The list is ordered by the proportion
of amino acids of each type that are
fully buried. What types of amino
acids are most commonly buried?
Least commonly buried? Are there any
surprises? If so, why?