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PDBsum entry 1u0n
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Blood clotting
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PDB id
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1u0n
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Contents |
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208 a.a.
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133 a.a.
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125 a.a.
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265 a.a.
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References listed in PDB file
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Key reference
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Title
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The snake venom protein botrocetin acts as a biological brace to promote dysfunctional platelet aggregation.
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Authors
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K.Fukuda,
T.Doggett,
I.J.Laurenzi,
R.C.Liddington,
T.G.Diacovo.
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Ref.
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Nat Struct Mol Biol, 2005,
12,
152-159.
[DOI no: ]
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PubMed id
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Abstract
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Botrocetin is a snake venom protein that enhances the affinity of the A1 domain
of plasma von Willebrand factor (vWF) for the platelet receptor glycoprotein
Ibalpha (GPIbalpha), an event that contributes to bleeding and host death. Here
we describe a kinetic and crystallographic analysis of this interaction that
reveals a novel mechanism of affinity enhancement. Using
high-temporal-resolution microscopy, we show that botrocetin decreases the
GPIbalpha off-rate two-fold in both human and mouse complexes without affecting
the on-rate. The key to this behavior is that, upon binding of GPIbalpha to
vWF-A1, botrocetin prebound to vWF-A1 makes no contacts initially with
GPIbalpha, but subsequently slides around the A1 surface to form a new
interface. This two-step mechanism and flexible coupling may prevent adverse
alterations in on-rate of GPIbalpha for vWF-A1, and permit adaptation to
structural differences in GPIbalpha and vWF in several prey species.
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Figure 5.
Figure 5. The effect of botrocetin on the kinetics of the GPIb
 -vWF-A1
tether bond. (a,b) Botrocetin does not enhance the cellular
on-rate for either the human or mouse GPIb  -vWF-A1
tether bond as observed for the type 2B mutation I546V. An
enhancement in cellular on-rate is denoted as an increase in
tethering frequency of protein-coated beads. Data represent mean
 s.d.
for three independent experiments. WT, wild type.
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Figure 7.
Figure 7. Proposed schematic model for the two-step mechanism of
interaction between the botrocetin -vWF-A1 binary complex and
GPIb .
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Mol Biol
(2005,
12,
152-159)
copyright 2005.
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