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| | ==Crystal structure of rhodocetin== | | ==Crystal structure of rhodocetin== |
| - | <StructureSection load='3gpr' size='340' side='right' caption='[[3gpr]], [[Resolution|resolution]] 3.20Å' scene=''> | + | <StructureSection load='3gpr' size='340' side='right'caption='[[3gpr]], [[Resolution|resolution]] 3.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3gpr]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Calloselasma_rhodostoma Calloselasma rhodostoma]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GPR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3GPR FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3gpr]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Calloselasma_rhodostoma Calloselasma rhodostoma]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GPR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GPR FirstGlance]. <br> |
| - | </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=3gpr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gpr OCA], [http://pdbe.org/3gpr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3gpr RCSB], [http://www.ebi.ac.uk/pdbsum/3gpr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3gpr ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.2Å</td></tr> |
| | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3gpr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gpr OCA], [https://pdbe.org/3gpr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gpr RCSB], [https://www.ebi.ac.uk/pdbsum/3gpr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gpr ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SLEA_CALRH SLEA_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:10360956</ref> <ref>PMID:11121411</ref> <ref>PMID:12871211</ref> [[http://www.uniprot.org/uniprot/SLEB_CALRH SLEB_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:10360956</ref> <ref>PMID:11121411</ref> <ref>PMID:12871211</ref> | + | [https://www.uniprot.org/uniprot/SLEA_CALRH SLEA_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:10360956</ref> <ref>PMID:11121411</ref> <ref>PMID:12871211</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gp/3gpr_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gp/3gpr_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | </div> | | </div> |
| | <div class="pdbe-citations 3gpr" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 3gpr" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Rhodocetin|Rhodocetin]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Calloselasma rhodostoma]] | | [[Category: Calloselasma rhodostoma]] |
| - | [[Category: Stetefeld, J]] | + | [[Category: Large Structures]] |
| - | [[Category: Cell adhesion]] | + | [[Category: Stetefeld J]] |
| - | [[Category: Disulfide bond]]
| + | |
| - | [[Category: Lectin]]
| + | |
| - | [[Category: Rhodocetin]]
| + | |
| - | [[Category: Secreted]]
| + | |
| - | [[Category: Toxin]]
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| Structural highlights
Function
SLEA_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.[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The integrin alpha2beta1 plays an important role in various pathophysiological processes, such as thrombosis, wound healing, inflammation, and metastasis. Rhodocetin, a constituent of the venom of the hemorrhagic Malayan pit viper (Calloselasma rhodostoma), is a specific alpha2beta1 integrin antagonist. To understand its molecular mode of action, its structure was studied by crystallography. Its quaternary structure in solution was also analyzed biochemically. Two novel subunits of rhodocetin were sequenced by mass spectrometry. Their integrin binding was measured by protein interaction ELISAs. Rhodocetin is a C-type lectin-like protein (CLP) consisting of four homologous, yet distinct, subunits, alpha, beta, gamma, and delta, the latter two of which have been unknown to date. With their CLP folds and loop-swapping motifs, the subunits alpha, beta and gamma, delta form two heterodimeric pairs. Uniquely, they arrange orthogonally and shape a cruciform molecule. Bearing a single unpaired cysteine residue, rhodocetin can only form covalent supramolecular complexes with a maximum aggregation number of 2, unlike many heterodimeric CLPs. Being the first heterotetrameric CLP to be crystallized, rhodocetin provides not only the prototypic molecular structure for heterotetrameric CLPs, but also a lead structure for pharmaceutical alpha2beta1 integrin antagonists.
The alpha2beta1 integrin-specific antagonist rhodocetin is a cruciform, heterotetrameric molecule.,Eble JA, Niland S, Bracht T, Mormann M, Peter-Katalinic J, Pohlentz G, Stetefeld J FASEB J. 2009 Sep;23(9):2917-27. Epub 2009 Apr 15. PMID:19369383[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Wang R, Kini RM, Chung MC. Rhodocetin, a novel platelet aggregation inhibitor from the venom of Calloselasma rhodostoma (Malayan pit viper): synergistic and noncovalent interaction between its subunits. Biochemistry. 1999 Jun 8;38(23):7584-93. PMID:10360956 doi:http://dx.doi.org/10.1021/bi982132z
- ↑ Eble JA, Beermann B, Hinz HJ, Schmidt-Hederich A. alpha 2beta 1 integrin is not recognized by rhodocytin but is the specific, high affinity target of rhodocetin, an RGD-independent disintegrin and potent inhibitor of cell adhesion to collagen. J Biol Chem. 2001 Apr 13;276(15):12274-84. Epub 2000 Dec 19. PMID:11121411 doi:http://dx.doi.org/10.1074/jbc.M009338200
- ↑ Eble JA, Tuckwell DS. The alpha2beta1 integrin inhibitor rhodocetin binds to the A-domain of the integrin alpha2 subunit proximal to the collagen-binding site. Biochem J. 2003 Nov 15;376(Pt 1):77-85. PMID:12871211 doi:http://dx.doi.org/10.1042/BJ20030373
- ↑ Eble JA, Niland S, Bracht T, Mormann M, Peter-Katalinic J, Pohlentz G, Stetefeld J. The alpha2beta1 integrin-specific antagonist rhodocetin is a cruciform, heterotetrameric molecule. FASEB J. 2009 Sep;23(9):2917-27. Epub 2009 Apr 15. PMID:19369383 doi:10.1096/fj.08-126763
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