title: Conformational dynamics of the F1-ATPase beta-subunit: a molecular dynamics study.
abstract: According to the different nucleotide occupancies of the F(1)-ATPase beta-subunits and due to the asymmetry imposed through the central gamma-subunit, the beta-subunit adopts different conformations in the crystal structures. Recently, a spontaneous and nucleotide-independent closure of the open beta-subunit upon rotation of the gamma-subunit has been proposed. To address the question whether this closure is dictated by interactions to neighbored subunits or whether the open beta-subunit behaves like a prestressed "spring," we report multinanosecond molecular dynamics simulations of the isolated beta-subunit with different start conformations and different nucleotide occupancies. We have observed a fast, spontaneous closure motion of the open beta(E)-subunit, consistent with the available x-ray structures. The motions and kinetics are similar to those observed in simulations of the full (alpha beta)(3)gamma-complex, which support the view of a prestressed "spring," i.e., that forces internal to the beta(E)-subunit dominate possible interactions from adjacent alpha-subunits. Additionally, nucleotide removal is found to trigger conformational transitions of the closed beta(TP)-subunit; this provides evidence that the recently resolved half-closed beta-subunit conformation is an intermediate state before product release. The observed motions provide a plausible explanation why ADP and P(i) are required for the release of bound ATP and why gamma-depleted (alpha beta)(3) has a drastically reduced hydrolysis rate.
authors.affiliation: Theoretical Molecular Biophysics Group, Max-Planck Institute for Biophysical Chemistry, Göttingen, Germany.
authors.forename: Rainer A
authors.initials: RA
authors.lastname: Böckmann
authors.forename: Helmut
authors.initials: H
authors.lastname: Grubmüller
mesh_terms: D000244:Adenosine Diphosphate / Q000737:chemistry; D000255:Adenosine Triphosphate / Q000737:chemistry; D001407:Bacillus / Q000201:enzymology; D001665:Binding Sites; D020134:Catalytic Domain; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000201:enzymology; D007700:Kinetics; D008274:Magnesium / Q000737:chemistry; D008958:Models, Molecular; D009068:Movement; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D006180:Proton-Translocating ATPases / Q000737:chemistry*; D012984:Software; D013050:Spectrometry, Fluorescence; D013997:Time Factors
chemical_list: D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D006180:Proton-Translocating ATPases; D008274:Magnesium