| Structural highlights
Function
[AGGB_CALRH] Elicits platelet aggregation by the binding to the C-type lectin domain family 1 member B (CLEC1B/CLEC2). Binding leads to tyrosine phosphorylation in the cytoplasmic tail of CLEC1B, which promotes the binding of spleen tyrosine kinase (Syk), subsequent activation of PLCgamma2, and platelet activation and aggregation. Binding to GPIbalpha (GP1BA) and alpha2/beta-1 (ITGA2/ITGB1) may also induce aggregation, but this is controversial.[1] [2] [3] [4] [5] [6] [7] [8]
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
Binding of the snake venom protein rhodocytin to CLEC-2, a receptor on the surface of human platelets, initiates a signaling cascade leading to platelet activation and aggregation. We have previously solved the structure of CLEC-2. The 2.4 A resolution crystal structure of rhodocytin presented here demonstrates that it is the first snake venom or other C-type lectin-like protein to assemble as a non-disulfide linked (alphabeta)(2) tetramer. Rhodocytin is highly adapted for interaction with CLEC-2 and displays a concave binding surface, which is highly complementary to the experimentally determined binding interface on CLEC-2. Using computational dynamic methods, surface electrostatic charge and hydrophobicity analyses, and protein-protein docking predictions, we propose that the (alphabeta)(2) rhodocytin tetramer induces clustering of CLEC-2 receptors on the platelet surface, which will trigger major signaling events resulting in platelet activation and aggregation.
Crystal structure of rhodocytin, a ligand for the platelet-activating receptor CLEC-2.,Watson AA, Eble JA, O'Callaghan CA Protein Sci. 2008 Sep;17(9):1611-6. Epub 2008 Jun 26. PMID:18583525[9]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Navdaev A, Clemetson JM, Polgar J, Kehrel BE, Glauner M, Magnenat E, Wells TN, Clemetson KJ. Aggretin, a heterodimeric C-type lectin from Calloselasma rhodostoma (Malayan pit viper), stimulates platelets by binding to alpha2beta1 integrin and glycoprotein Ib, activating Syk and phospholipase Cgamma 2, but does not involve the glycoprotein VI/Fc receptor gamma chain collagen receptor. J Biol Chem. 2001 Jun 15;276(24):20882-9. Epub 2001 Apr 3. PMID:11287424 doi:http://dx.doi.org/10.1074/jbc.M101585200
- ↑ Shin Y, Morita T. Rhodocytin, a functional novel platelet agonist belonging to the heterodimeric C-type lectin family, induces platelet aggregation independently of glycoprotein Ib. Biochem Biophys Res Commun. 1998 Apr 28;245(3):741-5. PMID:9588185 doi:http://dx.doi.org/10.1006/bbrc.1998.8516
- ↑ Wang R, Kong C, Kolatkar P, Chung MC. A novel dimer of a C-type lectin-like heterodimer from the venom of Calloselasma rhodostoma (Malayan pit viper). FEBS Lett. 2001 Nov 23;508(3):447-53. PMID:11728470
- ↑ Huang TF, Liu CZ, Yang SH. Aggretin, a novel platelet-aggregation inducer from snake (Calloselasma rhodostoma) venom, activates phospholipase C by acting as a glycoprotein Ia/IIa agonist. Biochem J. 1995 Aug 1;309 ( Pt 3):1021-7. PMID:7639679
- ↑ Chung CH, Peng HC, Huang TF. Aggretin, a C-type lectin protein, induces platelet aggregation via integrin alpha(2)beta(1) and GPIb in a phosphatidylinositol 3-kinase independent pathway. Biochem Biophys Res Commun. 2001 Jul 20;285(3):689-95. PMID:11453648 doi:http://dx.doi.org/10.1006/bbrc.2001.5228
- ↑ Bergmeier W, Bouvard D, Eble JA, Mokhtari-Nejad R, Schulte V, Zirngibl H, Brakebusch C, Fassler R, Nieswandt B. Rhodocytin (aggretin) activates platelets lacking alpha(2)beta(1) integrin, glycoprotein VI, and the ligand-binding domain of glycoprotein Ibalpha. J Biol Chem. 2001 Jul 6;276(27):25121-6. Epub 2001 May 14. PMID:11352922 doi:http://dx.doi.org/10.1074/jbc.M103892200
- ↑ Chung CH, Wu WB, Huang TF. Aggretin, a snake venom-derived endothelial integrin alpha 2 beta 1 agonist, induces angiogenesis via expression of vascular endothelial growth factor. Blood. 2004 Mar 15;103(6):2105-13. Epub 2003 Nov 20. PMID:14630793 doi:http://dx.doi.org/10.1182/blood-2003-07-2483
- ↑ Suzuki-Inoue K, Fuller GL, Garcia A, Eble JA, Pohlmann S, Inoue O, Gartner TK, Hughan SC, Pearce AC, Laing GD, Theakston RD, Schweighoffer E, Zitzmann N, Morita T, Tybulewicz VL, Ozaki Y, Watson SP. A novel Syk-dependent mechanism of platelet activation by the C-type lectin receptor CLEC-2. Blood. 2006 Jan 15;107(2):542-9. Epub 2005 Sep 20. PMID:16174766 doi:2005-05-1994
- ↑ Watson AA, Eble JA, O'Callaghan CA. Crystal structure of rhodocytin, a ligand for the platelet-activating receptor CLEC-2. Protein Sci. 2008 Sep;17(9):1611-6. Epub 2008 Jun 26. PMID:18583525 doi:10.1110/ps.035568.108
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