title: Cofilin cross-bridges adjacent actin protomers and replaces part of the longitudinal F-actin interface.
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.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095, USA. dkudryas@ucla.edu
authors.forename: D S
authors.initials: DS
authors.lastname: Kudryashov
authors.forename: V E
authors.initials: VE
authors.lastname: Galkin
authors.forename: A
authors.initials: A
authors.lastname: Orlova
authors.forename: M
authors.initials: M
authors.lastname: Phan
authors.forename: E H
authors.initials: EH
authors.lastname: Egelman
authors.forename: E
authors.initials: E
authors.lastname: Reisler
mesh_terms: D051339:Actin Depolymerizing Factors / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D000199:Actins / Q000235:genetics* / Q000378:metabolism* / Q000648:ultrastructure; D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D003545:Cysteine / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008854:Microscopy, Electron; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D010590:Phalloidine; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D011817:Rabbits; D012235:Rhodamines; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D013912:Threonine / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; D012235:Rhodamines; D010590:Phalloidine; D013912:Threonine; D000244:Adenosine Diphosphate; D003545:Cysteine