ANALOGOUS F-ACTIN BINDING BY COFILIN AND GELSOLIN SEGMENT-2 SUBSTANTIATES THEIR STRUCTURAL RELATIONSHIP

Cofilin is representative for a family of low molecular weight actin f ilament binding and depolymerizing proteins. Recently the three-dimens ional structure of yeast cofilin and of the cofilin homologs destrin a nd actophorin were resolved, and a striking similarity to segments of gelsolin and related proteins was observed (Hatanaka, H., Ogura, K., M oriyama, K., Ichikawa, S., Yahara, I., and Inagaka, F. (1996) Cell 85, 1047-1055; Fedorov, A. A., Lappalainen, P., Fedorov, E. V., Drubin, D . G., and Almo, S. C. (1997) Not. Struct. Biol. 4, 366-369; Leonard, S . A., Gittis, A. G., Petrella, E. C., Pollard, T. D., and Lattman, E. E. (1997) Not. Struct. Biol. 4, 369-373). Using peptide mimetics, we s how that the actin binding site stretches over the entire cofilin alph a-helix 112-128. In addition, we demonstrate that cofilin and its acti n binding peptide compete with gelsolin segments 2-3 for binding to ac tin filaments. Based on these competition data, we propose that cofili n and segment 2 of gelsolin use a common structural topology to bind t o actin and probably share a similar target site on the filament. This adds a functional dimension to their reported structural homology, an d this F-actin binding mode provides a basis to further enlighten the effect of members of the cofilin family on actin filament dynamics.