title: Conserved structural determinants in three-fingered protein domains.
abstract: The three-dimensional structures of some components of snake venoms forming so-called 'three-fingered protein' domains (TFPDs) are similar to those of the ectodomains of activin, bone morphogenetic protein and transforming growth factor-beta receptors, and to a variety of proteins encoded by the Ly6 and Plaur genes. The analysis of sequences of diverse snake toxins, various ectodomains of the receptors that bind activin and other cytokines, and numerous gene products encoded by the Ly6 and Plaur families of genes has revealed that they differ considerably from each other. The sequences of TFPDs may consist of up to six disulfide bonds, three of which have the same highly conserved topology. These three disulfide bridges and an asparagine residue in the C-terminal part of TFPDs are essential for the TFPD-like fold. Analyses of the three-dimensional structures of diverse TFPDs have revealed that the three highly conserved disulfides impose a major stabilizing contribution to the TFPD-like fold, in both TFPDs contained in some snake venoms and ectodomains of several cellular receptors, whereas the three remaining disulfide bonds impose specific geometrical constraints in the three fingers of some TFPDs.
authors.affiliation: Institut de Biologie et de Technologies de Saclay, SIMOPRO/DSV/CEA, Gif-sur-Yvette, France. galat@dsvidf.cea.fr
authors.forename: Andrzej
authors.initials: A
authors.lastname: Galat
authors.forename: Gregory
authors.initials: G
authors.lastname: Gross
authors.forename: Pascal
authors.initials: P
authors.lastname: Drevet
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sato
authors.forename: André
authors.initials: A
authors.lastname: Ménez
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D003553:Cystine / Q000737:chemistry; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009498:Neurotoxins / Q000737:chemistry; D054730:Protein Interaction Domains and Motifs; D011956:Receptors, Cell Surface / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D012910:Snake Venoms / Q000737:chemistry*
chemical_list: D008024:Ligands; D009498:Neurotoxins; D011956:Receptors, Cell Surface; D012910:Snake Venoms; D003553:Cystine