1fe8
From Proteopedia
(New page: 200px<br /> <applet load="1fe8" size="450" color="white" frame="true" align="right" spinBox="true" caption="1fe8, resolution 2.03Å" /> '''CRYSTAL STRUCTURE O...) |
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| - | [[Image:1fe8.gif|left|200px]]<br /> | + | [[Image:1fe8.gif|left|200px]]<br /><applet load="1fe8" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="1fe8, resolution 2.03Å" /> | caption="1fe8, resolution 2.03Å" /> | ||
'''CRYSTAL STRUCTURE OF THE VON WILLEBRAND FACTOR A3 DOMAIN IN COMPLEX WITH A FAB FRAGMENT OF IGG RU5 THAT INHIBITS COLLAGEN BINDING'''<br /> | '''CRYSTAL STRUCTURE OF THE VON WILLEBRAND FACTOR A3 DOMAIN IN COMPLEX WITH A FAB FRAGMENT OF IGG RU5 THAT INHIBITS COLLAGEN BINDING'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Von Willebrand factor (vWF) is a multimeric glycoprotein that mediates | + | Von Willebrand factor (vWF) is a multimeric glycoprotein that mediates platelet adhesion and thrombus formation at sites of vascular injury. vWF functions as a molecular bridge between collagen and platelet receptor glycoprotein Ib. The major collagen-binding site of vWF is contained within the A3 domain, but its precise location is unknown. To localize the collagen-binding site, we determined the crystal structure of A3 in complex with an Fab fragment of antibody RU5 that inhibits collagen binding. The structure shows that RU5 recognizes a nonlinear epitope consisting of residues 962-966, 981-997, and 1022-1026. Alanine mutants were constructed of residues Arg(963), Glu(987), His(990), Arg(1016), and His(1023), located in or close to the epitope. Mutants were expressed as fully processed multimeric vWF. Mutation of His(1023) abolished collagen binding, whereas mutation of Arg(963) and Arg(1016) reduced collagen binding by 25-35%. These residues are part of loops alpha3beta4 and alpha1beta2 and alpha-helix 3, respectively, and lie near the bottom face of the domain. His(1023) and flanking residues display multiple conformations in available A3-crystal structures, suggesting that binding of A3 to collagen involves an induced-fit mechanism. The collagen-binding site of A3 is located distant from the top face of the domain where collagen-binding sites are found in homologous integrin I domains. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1FE8 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with NAG and CAC as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1FE8 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=NAG:'>NAG</scene> and <scene name='pdbligand=CAC:'>CAC</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FE8 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Bouma, B.]] | [[Category: Bouma, B.]] | ||
[[Category: Gros, P.]] | [[Category: Gros, P.]] | ||
| - | [[Category: Huizinga, E | + | [[Category: Huizinga, E G.]] |
[[Category: Kroon, J.]] | [[Category: Kroon, J.]] | ||
| - | [[Category: Schiphorst, M | + | [[Category: Schiphorst, M E.]] |
| - | [[Category: Sixma, J | + | [[Category: Sixma, J J.]] |
[[Category: CAC]] | [[Category: CAC]] | ||
[[Category: NAG]] | [[Category: NAG]] | ||
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[[Category: von willebrand factor a-type domain]] | [[Category: von willebrand factor a-type domain]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:37:46 2008'' |
Revision as of 10:37, 21 February 2008
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CRYSTAL STRUCTURE OF THE VON WILLEBRAND FACTOR A3 DOMAIN IN COMPLEX WITH A FAB FRAGMENT OF IGG RU5 THAT INHIBITS COLLAGEN BINDING
Contents |
Overview
Von Willebrand factor (vWF) is a multimeric glycoprotein that mediates platelet adhesion and thrombus formation at sites of vascular injury. vWF functions as a molecular bridge between collagen and platelet receptor glycoprotein Ib. The major collagen-binding site of vWF is contained within the A3 domain, but its precise location is unknown. To localize the collagen-binding site, we determined the crystal structure of A3 in complex with an Fab fragment of antibody RU5 that inhibits collagen binding. The structure shows that RU5 recognizes a nonlinear epitope consisting of residues 962-966, 981-997, and 1022-1026. Alanine mutants were constructed of residues Arg(963), Glu(987), His(990), Arg(1016), and His(1023), located in or close to the epitope. Mutants were expressed as fully processed multimeric vWF. Mutation of His(1023) abolished collagen binding, whereas mutation of Arg(963) and Arg(1016) reduced collagen binding by 25-35%. These residues are part of loops alpha3beta4 and alpha1beta2 and alpha-helix 3, respectively, and lie near the bottom face of the domain. His(1023) and flanking residues display multiple conformations in available A3-crystal structures, suggesting that binding of A3 to collagen involves an induced-fit mechanism. The collagen-binding site of A3 is located distant from the top face of the domain where collagen-binding sites are found in homologous integrin I domains.
Disease
Known diseases associated with this structure: von Willebrand disease OMIM:[193400]
About this Structure
1FE8 is a Single protein structure of sequence from Homo sapiens and Mus musculus with and as ligands. Full crystallographic information is available from OCA.
Reference
Identification of the collagen-binding site of the von Willebrand factor A3-domain., Romijn RA, Bouma B, Wuyster W, Gros P, Kroon J, Sixma JJ, Huizinga EG, J Biol Chem. 2001 Mar 30;276(13):9985-91. Epub 2000 Nov 29. PMID:11098050
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