Cofilin cross-bridges adjacent actin protomers and replaces part of the longitudinal F-actin interface

J Mol Biol. 2006 May 5;358(3):785-97. doi: 10.1016/j.jmb.2006.02.029. Epub 2006 Feb 28.

Abstract

ADF/cofilins are abundant actin binding proteins critical to the survival of eukaryotic cells. Most ADF/cofilins bind both G and F-actin, sever the filaments and accelerate their treadmilling. These effects are linked to rearrangements of interprotomer contacts, changes in the mean twist, and filament destabilization by ADF/cofilin. Paradoxically, it was reported that under certain in vitro and in vivo conditions cofilin may stabilize actin filaments and nucleate their formation. Here, we show that yeast cofilin and human muscle cofilin (cofilin-2) accelerate the nucleation and elongation of ADP-F-actin and stabilize such filaments. Moreover, cofilin rescues the polymerization of the assembly incompetent tethramethyl rhodamine (TMR)-actin and T203C/C374S yeast mutant actin. Filaments of cofilin-decorated TMR-actin and unlabeled actin are indistinguishable, as revealed by electron microscopy and three-dimensional reconstruction. Our data suggest that ADF/cofilins play an active role in establishing new interprotomer interfaces in F-actin that substitute for disrupted (as in TMR-actin and mutant actin) or weakened (as in ADP-actin) longitudinal contacts in filaments.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Actin Depolymerizing Factors / genetics
  • Actin Depolymerizing Factors / metabolism*
  • Actin Depolymerizing Factors / ultrastructure
  • Actins / genetics*
  • Actins / metabolism*
  • Actins / ultrastructure
  • Adenosine Diphosphate / metabolism
  • Animals
  • Cysteine / genetics
  • Cysteine / metabolism
  • Humans
  • Microscopy, Electron
  • Models, Molecular
  • Mutation / genetics
  • Phalloidine
  • Promoter Regions, Genetic / genetics*
  • Protein Binding
  • Protein Structure, Quaternary
  • Rabbits
  • Rhodamines
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Threonine / genetics
  • Threonine / metabolism
  • Time Factors

Substances

  • Actin Depolymerizing Factors
  • Actins
  • Rhodamines
  • Phalloidine
  • Threonine
  • Adenosine Diphosphate
  • Cysteine