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1u0o

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(New page: 200px<br /><applet load="1u0o" size="450" color="white" frame="true" align="right" spinBox="true" caption="1u0o, resolution 2.70&Aring;" /> '''The mouse von Willeb...)
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[[Image:1u0o.gif|left|200px]]<br /><applet load="1u0o" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1u0o, resolution 2.70&Aring;" />
 
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'''The mouse von Willebrand Factor A1-botrocetin complex'''<br />
 
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==Overview==
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==The mouse von Willebrand Factor A1-botrocetin complex==
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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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<StructureSection load='1u0o' size='340' side='right'caption='[[1u0o]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
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== Structural highlights ==
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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='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='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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</table>
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== Function ==
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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.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/u0/1u0o_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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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].
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<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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==About this Structure==
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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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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].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15665869 15665869]
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</div>
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<div class="pdbe-citations 1u0o" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Bothrops jararaca]]
[[Category: Bothrops jararaca]]
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[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
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[[Category: Protein complex]]
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[[Category: Fukuda K]]
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[[Category: Fukuda, K.]]
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[[Category: Liddington RC]]
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[[Category: Liddington, R.C.]]
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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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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 03:45:12 2007''
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Current revision

The mouse von Willebrand Factor A1-botrocetin complex

PDB ID 1u0o

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