Complete structure of p97/valosin-containing protein reveals communication between nucleotide domains
- PMID: 12949490
- DOI: 10.1038/nsb972
Complete structure of p97/valosin-containing protein reveals communication between nucleotide domains
Abstract
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-kappa b pathway. Here we present the crystal structure of full-length Mus musculus p97/VCP in complex with a mixture of ADP and ADP-AlF(x) at a resolution of 4.7 A. 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 Zn(2+) occludes the central pore of the hexamer, suggesting that substrate does not thread through the pore of the molecule.
Similar articles
-
Nucleotide dependent motion and mechanism of action of p97/VCP.J Mol Biol. 2005 Mar 25;347(2):437-52. doi: 10.1016/j.jmb.2005.01.060. J Mol Biol. 2005. PMID: 15740751
-
Conformational changes of the multifunction p97 AAA ATPase during its ATPase cycle.Nat Struct Biol. 2002 Dec;9(12):950-7. doi: 10.1038/nsb872. Nat Struct Biol. 2002. PMID: 12434150
-
Central pore residues mediate the p97/VCP activity required for ERAD.Mol Cell. 2006 May 19;22(4):451-62. doi: 10.1016/j.molcel.2006.03.036. Mol Cell. 2006. PMID: 16713576
-
Structural and functional implications of phosphorylation and acetylation in the regulation of the AAA+ protein p97.Biochem Cell Biol. 2010 Feb;88(1):41-8. doi: 10.1139/o09-128. Biochem Cell Biol. 2010. PMID: 20130678 Review.
-
New ATPase regulators--p97 goes to the PUB.Int J Biochem Cell Biol. 2009 Dec;41(12):2380-8. doi: 10.1016/j.biocel.2009.05.017. Epub 2009 Jun 2. Int J Biochem Cell Biol. 2009. PMID: 19497384 Review.
Cited by
-
Structural and functional deviations in disease-associated p97 mutants.J Struct Biol. 2012 Aug;179(2):83-92. doi: 10.1016/j.jsb.2012.04.024. Epub 2012 May 8. J Struct Biol. 2012. PMID: 22579784 Free PMC article. Review.
-
Adapted ATPase domain communication overcomes the cytotoxicity of p97 inhibitors.J Biol Chem. 2018 Dec 28;293(52):20169-20180. doi: 10.1074/jbc.RA118.004301. Epub 2018 Oct 31. J Biol Chem. 2018. PMID: 30381397 Free PMC article.
-
Compounds activating VCP D1 ATPase enhance both autophagic and proteasomal neurotoxic protein clearance.Nat Commun. 2022 Jul 16;13(1):4146. doi: 10.1038/s41467-022-31905-0. Nat Commun. 2022. PMID: 35842429 Free PMC article.
-
Cryo-EM structure of dodecameric Vps4p and its 2:1 complex with Vta1p.J Mol Biol. 2008 Mar 21;377(2):364-77. doi: 10.1016/j.jmb.2008.01.009. Epub 2008 Jan 12. J Mol Biol. 2008. PMID: 18280501 Free PMC article.
-
Cleaning up in the endoplasmic reticulum: ubiquitin in charge.Nat Struct Mol Biol. 2014 Apr;21(4):325-35. doi: 10.1038/nsmb.2793. Nat Struct Mol Biol. 2014. PMID: 24699081 Free PMC article. Review.
Publication types
MeSH terms
Substances
Associated data
- Actions
LinkOut - more resources
Other Literature Sources
Molecular Biology Databases
Miscellaneous