3op8

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{{STRUCTURE_3op8| PDB=3op8 | SCENE= }}
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==Crystal structure of the domain V from beta2-glycoprotein I==
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===Crystal structure of the domain V from beta2-glycoprotein I===
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<StructureSection load='3op8' size='340' side='right' caption='[[3op8]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
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{{ABSTRACT_PUBMED_21179511}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3op8]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3OP8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3OP8 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1c1z|1c1z]], [[1qub|1qub]]</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">APOH, B2GPI ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<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=3op8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3op8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3op8 RCSB], [http://www.ebi.ac.uk/pdbsum/3op8 PDBsum]</span></td></tr>
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</table>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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BACKGROUND: beta2GPI is a major antigen for autoantibodies associated with antiphospholipid syndrome (APS), an autoimmune disease characterized by thrombosis and recurrent pregnancy loss. Only the dimeric form of beta2GPI generated by anti-beta2GPI antibodies is pathologically important, in contrast to monomeric beta2GPI which is abundant in plasma. PRINCIPAL FINDINGS: We created a dimeric inhibitor, A1-A1, to selectively target beta2GPI in beta2GPI/antibody complexes. To make this inhibitor, we isolated the first ligand-binding module from ApoER2 (A1) and connected two A1 modules with a flexible linker. A1-A1 interferes with two pathologically important interactions in APS, the binding of beta2GPI/antibody complexes with anionic phospholipids and ApoER2. We compared the efficiency of A1-A1 to monomeric A1 for inhibition of the binding of beta2GPI/antibody complexes to anionic phospholipids. We tested the inhibition of beta2GPI present in human serum, beta2GPI purified from human plasma and the individual domain V of beta2GPI. We demonstrated that when beta2GPI/antibody complexes are formed, A1-A1 is much more effective than A1 in inhibition of the binding of beta2GPI to cardiolipin, regardless of the source of beta2GPI. Similarly, A1-A1 strongly inhibits the binding of dimerized domain V of beta2GPI to cardiolipin compared to the monomeric A1 inhibitor. In the absence of anti-beta2GPI antibodies, both A1-A1 and A1 only weakly inhibit the binding of pathologically inactive monomeric beta2GPI to cardiolipin. CONCLUSIONS: Our results suggest that the approach of using a dimeric inhibitor to block beta2GPI in the pathological multivalent beta2GPI/antibody complexes holds significant promise. The novel inhibitor A1-A1 may be a starting point in the development of an effective therapeutic for antiphospholipid syndrome.
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==Function==
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A Novel Dimeric Inhibitor Targeting Beta2GPI in Beta2GPI/Antibody Complexes Implicated in Antiphospholipid Syndrome.,Kolyada A, Lee CJ, De Biasio A, Beglova N PLoS One. 2010 Dec 15;5(12):e15345. PMID:21179511<ref>PMID:21179511</ref>
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[[http://www.uniprot.org/uniprot/APOH_HUMAN APOH_HUMAN]] Binds to various kinds of negatively charged substances such as heparin, phospholipids, and dextran sulfate. May prevent activation of the intrinsic blood coagulation cascade by binding to phospholipids on the surface of damaged cells.
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[3op8]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3OP8 OCA].
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</div>
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:021179511</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Beglova, N.]]
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[[Category: Beglova, N]]
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[[Category: Biasio, A De.]]
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[[Category: Biasio, A De]]
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[[Category: Kolyada, A.]]
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[[Category: Kolyada, A]]
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[[Category: Lee, C J.]]
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[[Category: Lee, C J]]
[[Category: Anionic phospholipids binding]]
[[Category: Anionic phospholipids binding]]
[[Category: Antiphospholipid syndrome]]
[[Category: Antiphospholipid syndrome]]

Revision as of 07:23, 19 December 2014

Crystal structure of the domain V from beta2-glycoprotein I

3op8, resolution 1.90Å

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