title: Conformational changes of the multifunction p97 AAA ATPase during its ATPase cycle.
abstract: p97 (also called VCP), a member of the AAA ATPase family, is involved in several cellular processes, including membrane fusion and extraction of proteins from the endoplasmic reticulum for cytoplasmic degradation. We have studied the conformational changes that p97 undergoes during the ATPase cycle by cryo-EM and single-particle analysis. Three-dimensional maps show that the two AAA domains, D1 and D2, as well as the N-domains, experience conformational changes during ATP binding, ATP hydrolysis, P(i) release and ADP release. The N-domain is flexible in most nucleotide states except after ATP hydrolysis. The rings formed by D1 and D2 rotate with respect to each other, and the size of their axial openings fluctuates. Taken together, our results depict the movements that this and possibly other AAA ATPases can undergo during an ATPase cycle.
authors.affiliation: The Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Rouiller
authors.forename: Byron
authors.initials: B
authors.lastname: DeLaBarre
authors.forename: Andrew P
authors.initials: AP
authors.lastname: May
authors.forename: William I
authors.initials: WI
authors.lastname: Weis
authors.forename: Axel T
authors.initials: AT
authors.lastname: Brunger
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Milligan
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Wilson-Kubalek
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry* / Q000502:physiology / Q000648:ultrastructure*; D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D020285:Cryoelectron Microscopy; D021621:Imaging, Three-Dimensional; D008958:Models, Molecular; D009038:Motion; D009687:Nuclear Proteins / Q000737:chemistry* / Q000502:physiology / Q000648:ultrastructure*; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D017384:Sequence Deletion
chemical_list: D009687:Nuclear Proteins; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; C404942:p97 ATPase