5thp: Difference between revisions
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The | ==Rhodocetin in complex with the integrin alpha2-A domain== | ||
<StructureSection load='5thp' size='340' side='right' caption='[[5thp]], [[Resolution|resolution]] 3.01Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5thp]] is a 18 chain structure with sequence from [http://en.wikipedia.org/wiki/ ] and [http://en.wikipedia.org/wiki/Calloselasma_rhodostoma Calloselasma rhodostoma]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5THP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5THP FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=5thp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5thp OCA], [http://pdbe.org/5thp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5thp RCSB], [http://www.ebi.ac.uk/pdbsum/5thp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5thp ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/SLEC_CALRH SLEC_CALRH]] Potent inhibitor of collagen-induced platelet aggregation. It acts by binding to the integrin alpha2A domain and blocks collagen binding to integrin alpha-2/beta-1 (ITGA2/ITGB1). The gamma/delta subunits mainly contribute to this activity.<ref>PMID:11121411</ref> <ref>PMID:12871211</ref> [[http://www.uniprot.org/uniprot/ITA2_HUMAN ITA2_HUMAN]] Integrin alpha-2/beta-1 is a receptor for laminin, collagen, collagen C-propeptides, fibronectin and E-cadherin. It recognizes the proline-hydroxylated sequence G-F-P-G-E-R in collagen. It is responsible for adhesion of platelets and other cells to collagens, modulation of collagen and collagenase gene expression, force generation and organization of newly synthesized extracellular matrix. [[http://www.uniprot.org/uniprot/SLED_CALRH SLED_CALRH]] Potent inhibitor of collagen-induced platelet aggregation. It acts by binding to the integrin alpha2A domain and blocks collagen binding to integrin alpha-2/beta-1 (ITGA2/ITGB1). The gamma/delta subunits mainly contribute to this activity.<ref>PMID:11121411</ref> <ref>PMID:12871211</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The collagen binding integrin alpha2beta1 plays a crucial role in hemostasis, fibrosis, and cancer progression amongst others. It is specifically inhibited by rhodocetin (RC), a C-type lectin-related protein (CLRP) found in Malayan pit viper (Calloselasma rhodostoma) venom. The structure of RC alone reveals a heterotetramer arranged as an alphabeta and gammadelta subunit in a cruciform shape. RC specifically binds to the collagen binding A-domain of the integrin alpha2 subunit, thereby blocking collagen-induced platelet aggregation. However, until now, the molecular basis for this interaction has remained unclear. Here, we present the molecular structure of the RCgammadelta-alpha2A complex solved to 3.0 A resolution. Our findings show that RC undergoes a dramatic structural reorganization upon binding to alpha2beta1 integrin. Besides the release of the nonbinding RCalphabeta tandem, the RCgamma subunit interacts with loop 2 of the alpha2A domain as result of a dramatic conformational change. The RCdelta subunit contacts the integrin alpha2A domain in the "closed" conformation through its helix C. Combined with epitope-mapped antibodies, conformationally locked alpha2A domain mutants, point mutations within the alpha2A loop 2, and chemical modifications of the purified toxin protein, this molecular structure of RCgammadelta-alpha2A complex explains the inhibitory mechanism and specificity of RC for alpha2beta1 integrin. | |||
Dramatic and concerted conformational changes enable rhodocetin to block alpha2beta1 integrin selectively.,Eble JA, McDougall M, Orriss GL, Niland S, Johanningmeier B, Pohlentz G, Meier M, Karrasch S, Estevao-Costa MI, Martins Lima A, Stetefeld J PLoS Biol. 2017 Jul 13;15(7):e2001492. doi: 10.1371/journal.pbio.2001492., eCollection 2017 Jul. PMID:28704364<ref>PMID:28704364</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 5thp" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Calloselasma rhodostoma]] | |||
[[Category: McDougall, M]] | |||
[[Category: Orriss, G L]] | |||
[[Category: Stetefeld, J]] | |||
[[Category: C-type lectin]] | |||
[[Category: Cell adhesion]] | |||
[[Category: Coagulation]] | |||
[[Category: Integrin]] | |||
[[Category: Venom]] | |||