Nature Structural Biology10, 856 - 863 (2003)
Published online: 31 August 2003; | doi:10.1038/nsb972
Complete structure of p97/valosin-containing protein reveals communication between nucleotide domains
Byron DeLaBarre
& Axel T Brunger
Howard Hughes Medical Institute and Departments of Molecular and Cellular Physiology, Neurology and Neurological Sciences, and Stanford Synchrotron Radiation Laboratory, Stanford University, James H. Clark Center E300-C, 318 Campus Drive, Stanford, California, USA 94305-5432.
The ATPase p97/VCP affects multiple events within the cell. These events include the alteration of both nuclear and mitotic Golgi membranes, the dislocation of ubiquitylated proteins from the endoplasmic reticulum and regulation of the NF-b pathway. Here we present the crystal structure of full-length Mus musculus p97/VCP in complex with a mixture of ADP and ADP−AlFx at a resolution of 4.7 Å. This is the first complete hexameric structure of a protein containing tandem AAA (ATPases associated with a variety of cellular activities) domains. Comparison of the crystal structure and cryo-electron microscopy (EM) reconstructions reveals large conformational changes in the helical subdomains during the hydrolysis cycle. Structural and functional data imply a communication mechanism between the AAA domains. A Zn2+ occludes the central pore of the hexamer, suggesting that substrate does not thread through the pore of the molecule.
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b pathway. Here we present the crystal structure of full-length Mus musculus p97/VCP in complex with a mixture of ADP and ADP−AlFx at a resolution of 4.7 Å. This is the first complete hexameric structure of a protein containing tandem AAA (ATPases associated with a variety of cellular activities) domains. Comparison of the crystal structure and cryo-electron microscopy (EM) reconstructions reveals large conformational changes in the helical subdomains during the hydrolysis cycle. Structural and functional data imply a communication mechanism between the AAA domains. A Zn2+ occludes the central pore of the hexamer, suggesting that substrate does not thread through the pore of the molecule.
