title: Cloning and characterisation of three novel disintegrin precursors from the venoms of three Atheris species: Atheris chlorechis, Atheris nitschei and Atheris squamigera.
abstract: Snake venom constitutes one of the most complex mixtures of naturally-occurring toxic proteins/polypeptides and a large number of these possess very profound biological activities. Disintegrins, that are commonly found in viper venoms, are low molecular weight proteins that usually contain an -Arg-Gly-Asp- (-RGD-) motif that is known to be involved in cell adhesion ligand recognition, binding specifically to cell surface integrin receptors and also exhibiting platelet anti-aggregation activity. Here, we report for the first time, the successful cloning of three cDNAs encoding disintegrin precursors from lyophilised venom-derived libraries of Atheris chlorechis, Atheris nitschei and Atheris squamigera, respectively. All of these disintegrins belong to the short-coding class and all exhibit high degrees of structural identity, both in their amino acid sequences and in the arrangement of their functional domains. Mass spectrometric analyses of the HPLC-separated/in-gel digested venom proteins was performed to characterise the mature disintegrins as expressed in the venom proteome. Studies on both the structures and conserved sites within these disintegrins are of considerable theoretical interest in the field of biological evolution and in the development of new research tools or novel templates for drug design.
authors.affiliation: Natural Drug Discovery Group, School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, UK.
authors.forename: He
authors.initials: H
authors.lastname: Wang
authors.forename: Xiaole
authors.initials: X
authors.lastname: Chen
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Mei
authors.initials: M
authors.lastname: Zhou
authors.forename: Tianbao
authors.initials: T
authors.lastname: Chen
authors.forename: Chris
authors.initials: C
authors.lastname: Shaw
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003001:Cloning, Molecular; D019295:Computational Biology; D018076:DNA, Complementary / Q000096:biosynthesis; D019483:Disintegrins / Q000737:chemistry* / Q000302:isolation & purification; D008969:Molecular Sequence Data; D010974:Platelet Aggregation / Q000187:drug effects; D020543:Proteome / Q000737:chemistry / Q000235:genetics; D014757:Viper Venoms / Q000737:chemistry*; D017819:Viperidae / Q000145:classification / Q000378:metabolism*
chemical_list: D018076:DNA, Complementary; D019483:Disintegrins; D020543:Proteome; D014757:Viper Venoms
keywords: Disintegrin; Mass spectrometry; Molecular cloning; Platelet aggregation; Snake; Venom