Examples of Protein Structures with Specific Functions

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Examples of Protein Structures with Specific
Functions

• Immunoglobulins- bind foreign molecules,
  signals destruction (simple)
• Hemoglobin transports O2 to respiring tissue
  allosteric (more complex)
• Actin/myosin muscle action, mechanical energy
  (also complex)
• Several enzymes organic/physical chemistry in
  action

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Antibody binding is highly specific

• How is this specificity mediated?
• Complementarity receptor/ligand binding is
  essentially pattern recognition between two
  complementary surfaces.

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Take Note p 75
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VVP Fig 7-33
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sheets are linked by a disulfide bond
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Fv
Fab
binding sites
Fc
IgG molecule
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Lysozyme-antibody Fab fragment complex
antigen
binding site
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2 Views of the Complementarity Determining Regions
CDR loops
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VVP Fig 7-36
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Take Note p 75 VVP Fig 7-37
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VVP Fig 27-37 Take Note p 390
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VVP Fig 27-38 Take Note p 390
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Simple binding protein (binds doesnt
release) Immunoglobulin Complex binding
protein (binds then releases) Hemoglobin/Myoglobi
n allosteric regulation Motility protein in
which activity is modulated by multiple
binding/release events Actin/Myosin regulation
of contraction by Ca2 (striated
muscle) Ligand/substrate/cofactor/protein
binding is CENTRAL to activity of proteins. It
is determined by binding surface COMPLEMENTARITY.
Binding surfaces may be revealed by alterations
in protein conformation or covalent structure.
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Oxygen is transported to cells
which are remote from air

O2 is required in cells, in the mitochondria for
ATP production
aerobic metabolism
Glucose O2 ----------------------------gt ATP
CO2
oxidative phosphorylation
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Oxygen is transported down
a concentration gradient
pO2
torr
hemoglobin
myoglobin
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Normal Red Blood Cells have a flattened discoid
shape rather than a spherical shape
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
vs.
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
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proximal His
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heme
myoglobin
proximal His (bound to Fe2)
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Fraction of Mb bound to O2 at pO2 30 torr
pO2 in capillaries
P50 2.8 torr
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Myoglobin single subunit (homologous to
Hemoglobin beta subunit)
Hemoglobin Four homologous subunits 2 alpha 2
beta
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Non-cooperative binding
Cooperative binding
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About 25 of O2 delivered
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About 40 of O2 delivered
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Oxy-Hb R State
Deoxy-Hb T State
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Oxy-Hb R State high O2 affinity
Deoxy-Hb T State low O2 affinity
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Binding and Release of O2, BPG, CO2, H
See VVP Fig 7-13
Lungs
Capillaries
CO2
Respiring cells
Mitochondrion(O2) Mb
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b H146 is deprotonated in the R state
b H146
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The R to T transition brings b D94 close to b
H146. How does this affect pKa for b H146?
b H146
b D94
NH
CO
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Deoxy-Hb T State low O2 affinity
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adaptation to high altitude increased BPG
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adaptation to high altitude effect of increased
BPG on fractional saturation
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Normal Red Blood Cells
Sickled Red Blood Cells
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Hb A)
Normal hemoglobin (
deoxyhemoglobin
Oxy Hb A
T state
R state
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Sickle Hemoglobin (Hb S)
b E6V mutation on surface of Hb causes
aggregation of deoxy Hb
deoxy Hb S
Oxy Hb S
forms polymeric rods
in T state
R state
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Hemolysis of a Sickled Red Blood Cell
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Myosin
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myosin S1 fragment
heavy chain (ATP and actin binding domain and
lever domain)
light chains (part of lever domain)
C-terminus
N-terminus
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actin binding
myosin headpiece motor domain bound to ADP
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S1 lever domain detail
light chains show homology to calmodulin
Ca2 ions
essential light chain
regulatory light chain
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Calmodulin binding to target protein sequence
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regulation of myosin binding by Ca2
thick filament