Protein Structure and Function

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Chapter 4

• Protein Structure and Function

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Why are proteins important? Enzymes-DNA
polymerase, RNA polymerase, kinase, phosphatase,
pepsin Structure-collagen (skin, tendon, bone,
cartilage), microtubules, cytoskeleton Transport-h
emoglobin, transferrin Motor proteins-myosin
(muscle), kinesin (interacts with
microtubules) Storage-ovalbumin,
casein Signal-insulin, nerve growth factor (NGF)
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Why are proteins important? Receptors-rhodopsin,
insulin receptor Gene regulation-lactose
repressor Immunity-antibodies Special
purpose-glue proteins mussels attachment
threads pyriform silk attachment filaments
green fluorescent protein (GFP) emits green
light antifreeze protein fish Arctic and
Antarctic
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Flow of genetic information (chart)
replication
transcription
translation
Amino acid sequence determines protein shape
(conformation) Amino acid side chains can be
divided into POLAR and NONPOLAR Figure 4-1 4-2
4-3
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Protein folding is driven by amino acid
sequence Ionic bond-Glu (polar, -) and Lys
(polar, ) Van der Waals interactions-Val and
Ala Hydrogen bond-any amino acid because it
involves the backbone of the protein Figure 4-4
4-5
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Polar amino acids-exposed to water Nonpolar amino
acids-buried inside of the protein form
hydrophobic core Protein conformation is driven
by free energy (?G) minimization Specialized
proteins molecular chaperones assist in protein
folding
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Protein folding is very important Improper
folding can cause protein aggregation Alzheimer
disease Huntigton disease Prion increase in
beta sheet conformation in misfolded
proteins Figure 4-8
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Protein structure (Pauling and Corey) a helix- a
keratin in hair ß sheet-silkworm silk
fibroins a helix and ß sheet-common structures
because the hydrogen bonds holding them together
are formed between the protein backbone
(examples) Figure 4-10
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• Dragline and viscid silks are the strongest
• Other proteins tested collagen, mussel byssal
  fibers, resilin, elastin
• Material properties of silk can be attributed to
  protein structure
• helix-elasticity (GlyProGlyGlyXxx motif)
• sheet-strength (poly Ala and poly GlyAla)

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Collagen elastic protein found in connective
tissue 3 polypeptide chains (Gly every 3rd amino
acid) form triple helix Elastin more loose
structure, polypeptides are cross-linked, it
extends when stretched, can come back to its
original, relaxed form Figure 4-28
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Proteins spanning lipid bilayer 20 aa needed to
form a helix across the membrane Usually nonpolar
(hydrophobic) side chains-interact with
hydrocarbon chains of phospholipids Backbone more
hydrophilic-forms hydrogen bonds to stabilize the
helix Figure 4-15
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Coiled coil structure 2 a helices have nonpolar
amino acids facing one side The 2 helices twist
around each other and minimize contact with
water Examples keratin (skin), myosin
(muscle) Figure 4-16
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Beta sheets Antiparallel-each of the protein
chain runs in the opposite direction Parallel-each
protein chain runs in the same direction Form
ridged and pleated structures Figure 4-17
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Antifreeze protein found in insects Parallel beta
sheet The distance of hydroxyl groups corresponds
to water molecules in ice lattice it can bind to
ice crystals thus preventing their growth Figure
4-18
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Levels of protein organization 1 Amino acid
sequence 2 a helix and ß sheet 3 Three
dimensional conformation, includes a helix,
ß sheet, random coils, and loops 4 Complex of
one or more polypeptide chain Figure 4-19
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Protein families Serine proteases (serine is part
of the active site) protein cleaving enzymes
chymotrypsin, trypsin, elastase all have similar
amino acid sequences, three dimensional
structure, and conformation
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Each of the enzymes has distinct enzymatic
activities cleaving bonds between different types
of amino acids chymotripsin requires aromatic
or bulky non polar side chain trypsin lysine
or arginine elastase small uncharged side
chain Slight changes in structure of the enzyme
lead to different substrate specificity
(example) Figure 4-21
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Hemoglobin is a tetramer consisting of two a
subunits and two ß subunits heme is shown in
red Figure 4-23 Proteins can assemble into
Globins, filaments, sheets, spheres Figure 4-9
4-25
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Disulfide bonds Covalent bonds Do not change
protein conformation but stabilize it (atomic
stapler) S-S bonds can be broken by strong
reductants mercaptoethanol Oxidation-increasing
the oxygen content or decreasing hydrogen
content Reduction-decreasing oxygen content or
increasing hydrogen content (example) Fig 4-29
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Binding site-part of a protein associated with a
ligand Binding site is a very precise sequence of
amino acids This amino acid arrangement can form
non-covalent bonds with certain ligands (ionic
and hydrogen bonds) Figure 4-30 4-31
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Antibodies are proteins in the immune system
which have the ability to recognize antigens with
high specificity Heavy and light chains are
stabilized by disulfide bonds Variable regions
bind antigens Figure 4-32
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Lysozymes cuts polysaccharide chains in bacteria
cell walls Lysozymes are present in saliva and
tears This reaction of hydrolysis is
energetically favorable. Lysozyme lowers the
energy of activation. During this process,
substrate and enzyme will form a brief covalent
bond Figure 4-33 4-34