THE I LWEQ MODULE - A CONSERVED SEQUENCE THAT SIGNIFIES F-ACTIN BINDING IN FUNCTIONALLY DIVERSE PROTEINS FROM YEAST TO MAMMALS/

Talin is an actin-binding protein involved in integrin-mediated cell a dhesion and spreading, The C-terminal 197 amino acids of vertebrate ta lin are 45% similar to the C-terminal residues of Sla2, a yeast protei n implicated in polarized assembly of the yeast actin cytoskeleton. Ta lin is also homologous in this region to nematode talin, cellular slim e mold filopodin, and an Sla2 homolog from nematode, Analysis of the c onserved C-terminal sequences of these five proteins with BLOCK MAKER reveals a series of four blocks, which we name the I/LWEQ module after the conserved initial residues in each block, Experiments presented h ere show that the conserved protein domain represented by the I/LWEQ m odule competes quantitatively with native talin for binding to F-actin in vitro, Furthermore, the corresponding domain of Sla2 binds to both yeast and vertebrate F-actin in vitro, Mutation of one of the conserv ed residues in the fourth conserved block abolishes the interaction of the Sla2 I/LWEQ module with F-actin, These results establish the loca tion of an F-actin binding domain in native talin, demonstrate that di rect interaction of Sla2 with actin is a possible basis for its effect on the actin cytoskeleton in vivo, and define the I/LWEQ consensus as a new actin-binding motif.