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1u0o

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Revision as of 07:25, 9 January 2019

The mouse von Willebrand Factor A1-botrocetin complex

Structural highlights

1u0o is a 3 chain structure with sequence from Bothrops jararaca and Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	1auq, 1ijb, 1ijk, 1u0n
Gene:	VwF (LK3 transgenic mice)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[LECBA_BOTJA] Snaclec that activates platelets by targeting vWF/GPIb. Two-chain botrocetin forms an activated complex with vWF (by binding the A1 domain), and the complex then binds to platelet glycoprotein Ibalpha (GP1BA), resulting in platelet aggregation. There are two distinct forms of the von Willebrand factor-dependent platelet coagglutinin. The dimeric form is 34-times more active than the one-chain botrocetin in promoting vWF binding to platelets. [VWF_MOUSE] Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface receptor complex GPIb-IX-V. Also acts as a chaperone for coagulation factor VIII, delivering it to the site of injury, stabilizing its heterodimeric structure and protecting it from premature clearance from plasma (By similarity).[UniProtKB:P04275] [LECBB_BOTJA] Snaclec that activates platelets by targeting vWF/GPIb. Two-chain botrocetin forms an activated complex with vWF (by binding the A1 domain), and the complex then binds to platelet glycoprotein Ibalpha (GP1BA), resulting in platelet aggregation. There are two distinct forms of the von Willebrand factor-dependent platelet coagglutinin. The dimeric form is 34-times more active than the one-chain botrocetin in promoting vWF binding to platelets.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

The snake venom protein botrocetin acts as a biological brace to promote dysfunctional platelet aggregation.,Fukuda K, Doggett T, Laurenzi IJ, Liddington RC, Diacovo TG Nat Struct Mol Biol. 2005 Feb;12(2):152-9. Epub 2005 Jan 16. PMID:15665869^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Fukuda K, Doggett T, Laurenzi IJ, Liddington RC, Diacovo TG. The snake venom protein botrocetin acts as a biological brace to promote dysfunctional platelet aggregation. Nat Struct Mol Biol. 2005 Feb;12(2):152-9. Epub 2005 Jan 16. PMID:15665869 doi:10.1038/nsmb892

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1u0o"

@@ Line 3: / Line 3: @@
 <StructureSection load='1u0o' size='340' side='right' caption='[[1u0o]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1u0o]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/ ] and [http://en.wikipedia.org/wiki/Bothrops_jararaca Bothrops jararaca]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1U0O OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1U0O FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1u0o]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Bothrops_jararaca Bothrops jararaca] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1U0O OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1U0O FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1auq|1auq]], [[1ijb|1ijb]], [[1ijk|1ijk]], [[1u0n|1u0n]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">VwF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1u0o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1u0o OCA], [http://pdbe.org/1u0o PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1u0o RCSB], [http://www.ebi.ac.uk/pdbsum/1u0o PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1u0o ProSAT]</span></td></tr>
 </table>
@@ Line 13: / Line 14: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/u0/1u0o_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/u0/1u0o_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 33: / Line 34: @@
 </StructureSection>
 [[Category: Bothrops jararaca]]
+[[Category: Lk3 transgenic mice]]
 [[Category: Fukuda, K]]
 [[Category: Liddington, R C]]

1u0o

From Proteopedia

Revision as of 07:25, 9 January 2019

The mouse von Willebrand Factor A1-botrocetin complex

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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