3op8
From Proteopedia
(Difference between revisions)
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- | + | ==Crystal structure of the domain V from beta2-glycoprotein I== | |
- | + | <StructureSection load='3op8' size='340' side='right' caption='[[3op8]], [[Resolution|resolution]] 1.90Å' scene=''> | |
- | + | == Structural highlights == | |
+ | <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> | ||
+ | </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> | ||
+ | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1c1z|1c1z]], [[1qub|1qub]]</td></tr> | ||
+ | <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> | ||
+ | <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> | ||
+ | </table> | ||
+ | <div style="background-color:#fffaf0;"> | ||
+ | == Publication Abstract from PubMed == | ||
+ | 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. | ||
- | + | 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> | |
- | + | ||
- | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
- | + | </div> | |
- | + | == References == | |
- | == | + | <references/> |
- | + | __TOC__ | |
+ | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
- | [[Category: Beglova, N | + | [[Category: Beglova, N]] |
- | [[Category: Biasio, A De | + | [[Category: Biasio, A De]] |
- | [[Category: Kolyada, A | + | [[Category: Kolyada, A]] |
- | [[Category: Lee, C J | + | [[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
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