Premium
Two activities of cofilin, severing and accelerating directional depolymerization of actin filaments, are affected differentially by mutations around the actin‐binding helix
Author(s) -
Moriyama Kenji,
Yahara Ichiro
Publication year - 1999
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/18.23.6752
Subject(s) - cofilin , depolymerization , metropolitan area , actin , biology , actin cytoskeleton , microbiology and biotechnology , cytoskeleton , cell , chemistry , genetics , polymer chemistry , medicine , pathology
The biochemical activities of cofilin are controversial. We demonstrated that porcine cofilin severs actin filaments and accelerates monomer release at the pointed ends. At pH 7.1, 0.8 μM cofilin cut filaments (2.2 μM actin) about every 290 subunits and increased the depolymerization rate 6.4‐fold. A kink in the major α‐helix of cofilin is thought to constitute a contact site for actin. Side chain hydroxyl groups of Ser119, Ser120 and Tyr82 in cofilin form hydrogen bonds with main chain carbonyl moieties from the helix, causing the kink. We eliminated side chain hydroxyls by Ser→Ala and/or Tyr→Phe mutagenesis. Severing and depolymerization‐enhancing activities were reduced dramatically in an Ala120 mutant, whereas the latter was decreased in a Phe82 mutant with a relatively small effect on severing, suggesting different structural bases for the two activities of cofilin. The Ala120‐equivalent mutation in yeast cofilin affected cell growth, whereas that of the Phe82‐equivalent had no effect in yeast. These results indicate the physiological significance of the severing activity of cofilin that is brought about by the kink in the helix.