1u0o: Difference between revisions

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[[Image:1u0o.gif|left|200px]]<br /><applet load="1u0o" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

[[Image:1u0o.gif|left|200px]]<br /><applet load="1u0o" size="350" color="white" frame="true" align="right" spinBox="true"

caption="1u0o, resolution 2.70Å" />

'''The mouse von Willebrand Factor A1-botrocetin complex'''<br />

==Overview==

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.

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.

==About this Structure==

1U0O is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Bothrops_jararaca Bothrops jararaca] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=1U0O OCA].

1U0O is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Bothrops_jararaca Bothrops jararaca] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1U0O OCA].

==Reference==

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[[Category: Protein complex]]

[[Category: Fukuda, K.]]

[[Category: Liddington, R.C.]]

[[Category: Liddington, R C.]]

[[Category: c-type lectin fold]]

[[Category: protein-protein complex]]

[[Category: rossmann fold]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Wed Nov~~ 21 03:45:~~12 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:19:22 2008''

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@@ Line 1: / Line 1: @@
-[[Image:1u0o.gif|left|200px]]<br /><applet load="1u0o" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1u0o.gif|left|200px]]<br /><applet load="1u0o" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1u0o, resolution 2.70&Aring;" />
 '''The mouse von Willebrand Factor A1-botrocetin complex'''<br />
 ==Overview==
-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.
+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.
 ==About this Structure==
-U0O is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Bothrops_jararaca Bothrops jararaca] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1U0O OCA].
+U0O is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Bothrops_jararaca Bothrops jararaca] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1U0O OCA].
 ==Reference==
@@ Line 15: / Line 15: @@
 [[Category: Protein complex]]
 [[Category: Fukuda, K.]]
-[[Category: Liddington, R.C.]]
+[[Category: Liddington, R C.]]
 [[Category: c-type lectin fold]]
 [[Category: protein-protein complex]]
 [[Category: rossmann fold]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 03:45:12 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:19:22 2008''