Molecular cloning of disintegrins from Cerastes vipera and Macrovipera lebetina transmediterranea venom gland cDNA libraries: insight into the evolution of the snake venom integrin-inhibition system.
We report the cloning and sequence analysis of Cerastes vipera and Macrovipera lebetina transmediterranea cDNAs coding for short non-RGD (Arg-Gly-Asp) disintegrins and for dimeric disintegrin subunits. The mRNAs belong to the short-coding class, suggesting that these disintegrin mRNAs may be more widely distributed than previously thought. Our data also argue for a common ancestry of the mRNAs of short disintegrins and those coding for precursors of dimeric disintegrin chains. The Macrovipera lebetina transmediterranea dimeric disintegrin reported to inhibit the laminin-binding integrins alpha3beta1, alpha6beta1 and alpha7beta1 was analysed using a proteomic approach and was shown to bear MLD (Met-Leu-Asp) and VGD (Val-Gly-Asp) motifs. The results highlight the fact that disintegrins have evolved a restricted panel of integrin-blocking sequences that segregate with defined branches of the phylogenetic tree of the integrin alpha-chains, providing novel insights into the evolutionary adaptation of the snake venom antagonists to the ligand-binding sites of their target integrin receptors.
Sanz
Libia
L
Instituto de Biomedicina de Valencia, C.S.I.C., Jaume Roig 11, 46010 Valencia, Spain.
Bazaa
Amine
A
Marrakchi
Naziha
N
Pérez
Alicia
A
Chenik
Mehdi
M
Bel Lasfer
Zakaria
Z
El Ayeb
Mohamed
M
Calvete
Juan J
JJ
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D019281:Dimerization; D019483:Disintegrins / Q000737:chemistry / Q000235:genetics*; D019143:Evolution, Molecular; D015723:Gene Library; D016023:Integrins / Q000037:antagonists & inhibitors*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000032:analysis / Q000737:chemistry; D016415:Sequence Alignment; D013057:Spectrum Analysis; D014757:Viper Venoms / Q000235:genetics*; D017819:Viperidae / Q000235:genetics* / Q000378:metabolism*
D018076:DNA, Complementary; D019483:Disintegrins; D016023:Integrins; D009842:Oligopeptides; D014757:Viper Venoms; C047981:arginyl-glycyl-aspartic acid