1u0o

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<StructureSection load='1u0o' size='340' side='right'caption='[[1u0o]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
<StructureSection load='1u0o' size='340' side='right'caption='[[1u0o]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<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://proteopedia.org/fgij/fg.htm?mol=1U0O FirstGlance]. <br>
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<table><tr><td colspan='2'>[[1u0o]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Bothrops_jararaca Bothrops jararaca] and [https://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]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1U0O FirstGlance]. <br>
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</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1auq|1auq]], [[1ijb|1ijb]], [[1ijk|1ijk]], [[1u0n|1u0n]]</div></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7&#8491;</td></tr>
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<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>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1u0o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1u0o OCA], [https://pdbe.org/1u0o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1u0o RCSB], [https://www.ebi.ac.uk/pdbsum/1u0o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1u0o ProSAT]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/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>
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</table>
</table>
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/LECBA_BOTJA 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. [[http://www.uniprot.org/uniprot/VWF_MOUSE 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] [[http://www.uniprot.org/uniprot/LECBB_BOTJA 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.
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[https://www.uniprot.org/uniprot/SLEA_BOTJA SLEA_BOTJA] Snaclec that binds to von Willebrand factor (VWF) and induces its interaction with GPIbalpha (GP1BA) (via the vWF A1 domain), resulting in platelet aggregation.
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1u0o ConSurf].
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1u0o ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
 
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== Publication Abstract from PubMed ==
 
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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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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<ref>PMID:15665869</ref>
 
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 
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</div>
 
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<div class="pdbe-citations 1u0o" style="background-color:#fffaf0;"></div>
 
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==See Also==
 
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*[[Von Willebrand factor 3D structures|Von Willebrand factor 3D structures]]
 
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== References ==
 
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<references/>
 
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Bothrops jararaca]]
[[Category: Bothrops jararaca]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Lk3 transgenic mice]]
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[[Category: Mus musculus]]
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[[Category: Fukuda, K]]
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[[Category: Fukuda K]]
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[[Category: Liddington, R C]]
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[[Category: Liddington RC]]
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[[Category: Blood clotting]]
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[[Category: C-type lectin fold]]
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[[Category: Protein-protein complex]]
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[[Category: Rossmann fold]]
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Revision as of 08:46, 1 May 2024

The mouse von Willebrand Factor A1-botrocetin complex

PDB ID 1u0o

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