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4r9w

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Revision as of 09:03, 22 November 2017

Crystal structure of platelet factor 4 complexed with fondaparinux

Structural highlights

4r9w is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	4r97, 4r9y
Gene:	PF4, CXCL4, SCYB4 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[PLF4_HUMAN] Released during platelet aggregation. Neutralizes the anticoagulant effect of heparin because it binds more strongly to heparin than to the chondroitin-4-sulfate chains of the carrier molecule. Chemotactic for neutrophils and monocytes. Inhibits endothelial cell proliferation, the short form is a more potent inhibitor than the longer form.^[1]

Publication Abstract from PubMed

Heparin-induced thrombocytopenia (HIT) is an autoimmune thrombotic disorder caused by immune complexes containing platelet factor 4 (PF4), antibodies to PF4 and heparin or cellular glycosaminoglycans (GAGs). Here we solve the crystal structures of the: (1) PF4 tetramer/fondaparinux complex, (2) PF4 tetramer/KKO-Fab complex (a murine monoclonal HIT-like antibody) and (3) PF4 monomer/RTO-Fab complex (a non-HIT anti-PF4 monoclonal antibody). Fondaparinux binds to the 'closed' end of the PF4 tetramer and stabilizes its conformation. This interaction in turn stabilizes the epitope for KKO on the 'open' end of the tetramer. Fondaparinux and KKO thereby collaborate to 'stabilize' the ternary pathogenic immune complex. Binding of RTO to PF4 monomers prevents PF4 tetramerization and inhibits KKO and human HIT IgG-induced platelet activation and platelet aggregation in vitro, and thrombus progression in vivo. The atomic structures provide a basis to develop new diagnostics and non-anticoagulant therapeutics for HIT.

Atomic description of the immune complex involved in heparin-induced thrombocytopenia.,Cai Z, Yarovoi SV, Zhu Z, Rauova L, Hayes V, Lebedeva T, Liu Q, Poncz M, Arepally G, Cines DB, Greene MI Nat Commun. 2015 Sep 22;6:8277. doi: 10.1038/ncomms9277. PMID:26391892^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Gupta SK, Hassel T, Singh JP. A potent inhibitor of endothelial cell proliferation is generated by proteolytic cleavage of the chemokine platelet factor 4. Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7799-803. PMID:7644496
↑ Cai Z, Yarovoi SV, Zhu Z, Rauova L, Hayes V, Lebedeva T, Liu Q, Poncz M, Arepally G, Cines DB, Greene MI. Atomic description of the immune complex involved in heparin-induced thrombocytopenia. Nat Commun. 2015 Sep 22;6:8277. doi: 10.1038/ncomms9277. PMID:26391892 doi:http://dx.doi.org/10.1038/ncomms9277

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4r9w"

@@ Line 1: / Line 1: @@
 ==Crystal structure of platelet factor 4 complexed with fondaparinux==
 <StructureSection load='4r9w' size='340' side='right' caption='[[4r9w]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4r9w]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R9W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4R9W FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4r9w]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R9W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4R9W FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NTO:TRISULFOAMINO+HEPARIN+PENTASACCHARIDE'>NTO</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4r97|4r97]], [[4r9y|4r9y]]</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=4r9w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r9w OCA], [http://pdbe.org/4r9w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4r9w RCSB], [http://www.ebi.ac.uk/pdbsum/4r9w PDBsum]</span></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PF4, CXCL4, SCYB4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4r9w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r9w OCA], [http://pdbe.org/4r9w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4r9w RCSB], [http://www.ebi.ac.uk/pdbsum/4r9w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4r9w ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 22: / Line 24: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Cai, Z]]
 [[Category: Greene, M I]]

4r9w

From Proteopedia

Revision as of 09:03, 22 November 2017

Crystal structure of platelet factor 4 complexed with fondaparinux

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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