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Updated: Jul 31, 2026
10:39
Visualization of ATP Synthase Dimers in Mitochondria by Electron Cryo-tomography
Published on: September 14, 2014
Structure of the AAA ATPase p97.
1Molecular Structure and Function Laboratory, Imperial Cancer Research Fund, London SW7 2AY, United Kingdom.
Molecular Cell
|February 13, 2001
Summary
p97 ATPase, crucial for membrane fusion, disassembles SNARE complexes. Structural analysis reveals its D1 and D2 hexamers pack tail-to-tail, suggesting a ratchet mechanism for ATP hydrolysis.
Area of Science:
- Molecular Biology
- Structural Biology
- Biochemistry
Background:
- p97 (also known as Valosin-Containing Protein) is a highly abundant AAA+ ATPase.
- It plays a critical role in various cellular processes, including homotypic membrane fusion.
- p97 is implicated in the disassembly of SNARE complexes, essential for membrane fusion events.
Purpose of the Study:
- To elucidate the structural basis of p97 function in membrane fusion.
- To investigate the conformational changes of p97 during its ATPase cycle.
Main Methods:
- X-ray crystallography was used to determine the structure of murine p97 N-terminal and D1 ATPase domains at 2.9 Å resolution.
- Cryo-electron microscopy (cryo-EM) was employed to resolve the structure of full-length rat p97 at 18 Å resolution.
Main Results:
- The structures reveal a tail-to-tail arrangement of the D1 and D2 ATPase hexamers in p97.
- The N-terminal domain was observed to be flexible.
- Comparison with NSF D2 (ATP complex) suggests ATP hydrolysis induces conformational changes in p97.
Conclusions:
- The observed D1 and D2 hexamer packing arrangement supports a proposed ratchet mechanism for p97's ATP hydrolysis cycle.
- Understanding p97's structure and mechanism provides insights into the regulation of membrane fusion.
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