title: Allostery of actin filaments: molecular dynamics simulations and coarse-grained analysis.
abstract: The structural and mechanical properties of monomeric actin (G-actin), the trimer nucleus, and actin filaments (F-actins) are determined as a function of the conformation of the DNase I-binding loop (DB loop) by using all-atom molecular dynamics simulations and coarse-grained (CG) analysis. Recent x-ray structures of ADP-bound G-actin (G-ADP) by Otterbein et al. [Otterbein, L. R., Graceffa, P. & Dominguez, R. (2001) Science 293, 708-711] and ATP-bound G-actin (G-ATP) by Graceffa and Dominguez [Graceffa, P. & Dominguez, R. (2003) J. Biol. Chem. 278, 34172-34180] indicate that the DB loop of actin does not have a well defined secondary structure in the ATP state but folds into an alpha-helix in the ADP state. MD simulations and CG analysis indicate that such a helical DB loop significantly weakens the intermonomer interactions of actin assemblies and thus leads to a wider, shorter, and more disordered filament. The computed persistence lengths of F-actin composed of G-ATP (16 microm) and of G-ADP (8.5 microm) agree well with the experimental values for the two states. Therefore, the loop-to-helix transition of the DB loop may be one of the factors that lead to the changes in structural and mechanical properties of F-actin after ATP hydrolysis. This result may provide a direct connection between the conformational changes of an actin monomer and the structural and mechanical properties of the cytoskeleton. The information provided by MD simulations also helps to understand the possible origin of the special features of actin dynamics.
authors.affiliation: Center for Biophysical Modeling and Simulation and Department of Chemistry, University of Utah, 315 South 1400 East, Room 2020, Salt Lake City, UT 84112-0850, USA.
authors.forename: Jhih-Wei
authors.initials: JW
authors.lastname: Chu
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Voth
mesh_terms: D008841:Actin Cytoskeleton / Q000737:chemistry*; D000199:Actins / Q000737:chemistry; D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000737:chemistry; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D000495:Allosteric Site; D000818:Animals; D001665:Binding Sites; D003198:Computer Simulation; D003850:Deoxyribonuclease I; D006801:Humans; D008958:Models, Molecular; D009038:Motion; D011485:Protein Binding; D017433:Protein Structure, Secondary
chemical_list: C042634:ADP-G-actin; C022920:ATP-G-actin; D000199:Actins; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D003850:Deoxyribonuclease I