Conformational changes of the multifunction p97 AAA ATPase during its ATPase cycle

• Published in: Nature structural & molecular biology Vol. 9; no. 12; pp. 950 - 957
• Main Authors: Wilson-Kubalek, Elizabeth M, Rouiller, Isabelle, DeLaBarre, Byron, May, Andrew P, Weis, William I, Brunger, Axel T, Milligan, Ronald A
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.12.2002
• Subjects: Adenosine Triphosphatases - chemistry; Adenosine Triphosphatases - physiology; Adenosine Triphosphatases - ultrastructure; Adenosine Triphosphate - chemistry; Adenosine Triphosphate - metabolism; Cryoelectron Microscopy; Imaging, Three-Dimensional; Models, Molecular; Motion; Nuclear Proteins - chemistry; Nuclear Proteins - physiology; Nuclear Proteins - ultrastructure; Protein Conformation; Protein Structure, Tertiary; Sequence Deletion
• ISSN: 1072-8368; 1545-9993; 2331-365X; 1545-9985
• DOI: 10.1038/nsb872

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.