title: Actin filament remodeling by actin depolymerization factor/cofilin.
abstract: We investigate, using molecular dynamics, how the severing protein, actin depolymerization factor (ADF)/cofilin, modulates the structure, conformational dynamics, and mechanical properties of actin filaments. The actin and cofilactin filament bending stiffness and corresponding persistence lengths obtained from all-atom simulations are comparable to values obtained from analysis of thermal fluctuations in filament shape. Filament flexibility is strongly affected by the nucleotide-linked conformation of the actin subdomain 2 DNase-I binding loop and the filament radial mass density distribution. ADF/cofilin binding between subdomains 1 and 3 of a filament subunit triggers reorganization of subdomain 2 of the neighboring subunit such that the DNase-I binding loop (DB-loop) moves radially away from the filament. Repositioning of the neighboring subunit DB-loop significantly weakens subunit interactions along the long-pitch helix and lowers the filament bending rigidity. Lateral filament contacts between the hydrophobic loop and neighboring short-pitch helix monomers in native filaments are also compromised with cofilin binding. These works provide a molecular interpretation of biochemical solution studies documenting the disruption of filament subunit interactions and also reveal the molecular basis of actin filament allostery and its linkage to ADF/cofilin binding.
authors.affiliation: Department of Chemical Engineering, University of Washington, Box 351750, Seattle, WA 98195-1750, USA.
authors.forename: Jim
authors.initials: J
authors.lastname: Pfaendtner
authors.forename: Enrique M
authors.initials: EM
authors.lastname: De La Cruz
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Voth
mesh_terms: D008841:Actin Cytoskeleton / Q000737:chemistry*; D051339:Actin Depolymerizing Factors / Q000737:chemistry; D000199:Actins / Q000737:chemistry*; D000818:Animals; D001671:Biochemistry / Q000379:methods; D001704:Biopolymers / Q000737:chemistry; D002417:Cattle; D051338:Cofilin 1 / Q000737:chemistry*; D003198:Computer Simulation; D003599:Cytoskeleton / Q000378:metabolism; D003850:Deoxyribonuclease I / Q000737:chemistry; D006358:Hot Temperature; D008958:Models, Molecular; D015233:Models, Statistical; D008968:Molecular Conformation; D011485:Protein Binding; D013696:Temperature
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; D001704:Biopolymers; D051338:Cofilin 1; D003850:Deoxyribonuclease I