Chapter 3 - Proteins

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Chapter 3 - Proteins
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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.

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Also Pro, Phe, Met, Trp, Gly, Cys
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Reactions that promote protein folding
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Adapted from L. Wu et al., 1995, Nature Struc.
Biol. 2281 courtesy of J. Harris and P. S. Kim
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Molecular chaperones Chaperones Video
chaperone-aided protein folding
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• Average length 10 residues 15 Å.
• Minimum length 4 residues how many H-bonds?
• Maximum length 40 residues.

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• Pleated - look edge-on
• Strands 5 Å apart
• Note direction of H-bonds will differ in
  anti-parallel mixed sheets

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• Loops Turns
• Connect secondary structural elements.
• Loops often carry the functional groups.
• Hairpin turns Shortest possible loops (2
  residues).
• Gly often in tight turns.

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Motifs (protein folds)
Domains/Modules
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
Pyruvate kinase
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• B sheet core with protruding loops
• Loops for binding interactions
• N and C terminals at opposite poles or form
  plug-ins

Domain shuffling
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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
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Serine Protease family
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Other Important Protein Structural Features

• Subunits
• Dimers, tetramers, large assemblies of monomers
• Filamentous proteins
• Globular proteins

Video clathrin assembly
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Test Your Knowledge Now
Amino Acid Side Chain Proportion Buried
I Ile 0.60
VVal 0.54
CCys 0.50
FPhe 0.50
LLeu 0.45
MMet 0.40
AAla 0.38
GGly 0.36
WTrp 0.27
TThr 0.23
SSer 0.22
EGlu 0.18
PPro 0.18
HHis 0.17
DAsp 0.15
YTyr 0.15
NAsn 0.12
QGln 0.07
KLys 0.03
RArg 0.01

• 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?

Table 1. Proportions of amino acids that are
inaccessible to solvent in a study of twelve
proteins.