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Conserved structural determinants in three‐fingered protein domains
Author(s) -
Galat Andrzej,
Gross Gregory,
Drevet Pascal,
Sato Atsushi,
Ménez André
Publication year - 2008
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2008.06473.x
Subject(s) - disulfide bond , biology , receptor , gene , activin type 2 receptors , computational biology , genetics , microbiology and biotechnology , superfamily , biochemistry
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‐β 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.