title: Molecular dynamics simulation and coarse-grained analysis of the Arp2/3 complex.
abstract: A molecular dynamics investigation and coarse-grained analysis of inactivated actin-related protein (Arp) 2/3 complex is presented. It was found that the nucleotide binding site within Arp3 remained in a closed position with bound ATP or ADP, but opened when simulation with no nucleotide was performed. In contrast, simulation of the isolated Arp3 subunit with bound ATP, showed a fast opening of the nucleotide binding cleft. A homology model for the missing subdomains 1 and 2 of Arp2 was constructed, and it was also found that the Arp2 binding cleft remained closed with bound nucleotide. Within the nucleotide binding cleft a distinct opening and closing period of 10 ns was observed in many of the simulations of Arp2/3 as well as isolated Arp3. Substitution studies were employed, and several alanine substitutions were found to induce a partial opening of the ATP binding cleft in Arp3 and Arp2, whereas only a single substitution was found to induce opening of the ADP binding cleft. It was also found that the nucleotide type did not cause a substantial change on interfacial contacts between Arp3 and the ArpC2, ArpC3 and ArpC4 subunits. Nucleotide-free Arp3 had generally less stable contacts, but the overall contact architecture was constant. Finally, nucleotide-dependent coarse-grained models for Arp3 are developed that serve to further highlight the structural differences induced in Arp3 by nucleotide hydrolysis.
authors.affiliation: Department of Chemistry, Center for Biophysical Modeling and Simulation, University of Utah, Salt Lake City, Utah 84112-0850, USA.
authors.forename: Jim
authors.initials: J
authors.lastname: Pfaendtner
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Voth
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D008958:Models, Molecular; D009154:Mutation; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013997:Time Factors
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate