Snake venom disintegrins: evolution of structure and function.
Disintegrins represent a family of polypeptides present in the venoms of various vipers that selectively block the function of integrin receptors. Here, we review our current view and hypothesis on the emergence and the structural and functional diversification of disintegrins by accelerated evolution and the selective loss of disulfide bonds of duplicated genes. Research on disintegrins is relevant for understanding the biology of viper venom toxins, but also provides information on new structural determinants involved in integrin recognition that may be useful in basic and clinical research. The role of the composition, conformation, and dynamics of the integrin inhibitory loop acting in concert with the C-terminal tail in determining the selective inhibition of integrin receptors is discussed.
Calvete
Juan J
JJ
Instituto de Biomedicina de Valencia, C.S.I.C., Jaume Roig 11, 46010 Valencia, Spain. jcalvete@ibv.csic.es
Marcinkiewicz
Cezary
C
Monleón
Daniel
D
Esteve
Vicent
V
Celda
Bernardo
B
Juárez
Paula
P
Sanz
Libia
L
D020816:Amino Acid Motifs / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019483:Disintegrins / Q000737:chemistry* / Q000145:classification / Q000235:genetics*; D019143:Evolution, Molecular; D020131:Genes, Duplicate; D016023:Integrins / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D012910:Snake Venoms / Q000378:metabolism*; D012911:Snakes; D013329:Structure-Activity Relationship
D019483:Disintegrins; D016023:Integrins; D012910:Snake Venoms