The crystal structure of murine p97/VCP at 3.6 Å

Trevor Huyton; Valerie E. Pye; Louise C. Briggs; Terence C. Flynn; Fabienne Beuron; Hisao Kondo; Jianpeng Ma; Xiaodong Zhang; Paul S. Freemont

doi:10.1016/j.jsb.2003.10.007

The crystal structure of murine p97/VCP at 3.6 Å

Trevor Huyton, Valerie E. Pye, Louise C. Briggs, Terence C. Flynn, Fabienne Beuron, Hisao Kondo, Jianpeng Ma, Xiaodong Zhang, Paul S. Freemont

Research output: Contribution to journal › Article › peer-review

160 Citations (Scopus)

Abstract

p97/VCP is a member of the AAA ATPase family and has roles in both membrane fusion and ubiquitin dependent protein degradation. Here, we present a 3.6Å crystal structure of murine p97 in which D2 domain has been modelled as poly-alanine and the remaining ~100 residues are absent. The resulting structure illustrates a head-to-tail packing arrangement of the two p97 AAA domains in a natural hexameric state with D1 ADP bound and D2 nucleotide free. The head-to-tail packing arrangement observed in this structure is in contrast to our previously predicted tail-to-tail packing model. The linker between the D1 and D2 domains is partially disordered, suggesting a flexible nature. Normal mode analysis of the crystal structure suggests anti-correlated motions and distinct conformational states of the two AAA domains.

Original language	English
Pages (from-to)	337-348
Number of pages	12
Journal	Journal of structural biology
Volume	144
Issue number	3
DOIs	https://doi.org/10.1016/j.jsb.2003.10.007
Publication status	Published - Dec 2003
Externally published	Yes

All Science Journal Classification (ASJC) codes

Structural Biology

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10.1016/j.jsb.2003.10.007

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@article{95ae7baae4d54747b154113bcb75f0b8,

title = "The crystal structure of murine p97/VCP at 3.6 {\AA}",

abstract = "p97/VCP is a member of the AAA ATPase family and has roles in both membrane fusion and ubiquitin dependent protein degradation. Here, we present a 3.6{\AA} crystal structure of murine p97 in which D2 domain has been modelled as poly-alanine and the remaining ~100 residues are absent. The resulting structure illustrates a head-to-tail packing arrangement of the two p97 AAA domains in a natural hexameric state with D1 ADP bound and D2 nucleotide free. The head-to-tail packing arrangement observed in this structure is in contrast to our previously predicted tail-to-tail packing model. The linker between the D1 and D2 domains is partially disordered, suggesting a flexible nature. Normal mode analysis of the crystal structure suggests anti-correlated motions and distinct conformational states of the two AAA domains.",

author = "Trevor Huyton and Pye, {Valerie E.} and Briggs, {Louise C.} and Flynn, {Terence C.} and Fabienne Beuron and Hisao Kondo and Jianpeng Ma and Xiaodong Zhang and Freemont, {Paul S.}",

note = "Funding Information: We are grateful to Tony Shaw, Pawel Dokurno, and Richard Newman for their earlier contributions, Ingrid Dreveny, and Hajime Niwa for fruitful discussions, Suhail Islam for helping with the graphics. T.H. wishes to thank E. Dodson and G. Murshadov of University of York for helpful discussions. T.H. was funded by Cancer Research UK. J.M. acknowledges financial support from the Robert A. Welch Foundation (Q-1512), the American Heart Association (AHA-TX0160107Y), the National Institute of Health (R01-GM067801), and a National Science Foundation Career Award (MCB-0237796). J.M. received the Award for Distinguished Young Scholars Abroad from the National Natural Science Foundation of China. X.Z. and P.F. wish to thank the Wellcome Trust for their generous funding.",

year = "2003",

month = dec,

doi = "10.1016/j.jsb.2003.10.007",

language = "English",

volume = "144",

pages = "337--348",

journal = "Journal of structural biology",

issn = "1047-8477",

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T1 - The crystal structure of murine p97/VCP at 3.6 Å

AU - Huyton, Trevor

AU - Pye, Valerie E.

AU - Briggs, Louise C.

AU - Flynn, Terence C.

AU - Beuron, Fabienne

AU - Kondo, Hisao

AU - Ma, Jianpeng

AU - Zhang, Xiaodong

AU - Freemont, Paul S.

N1 - Funding Information: We are grateful to Tony Shaw, Pawel Dokurno, and Richard Newman for their earlier contributions, Ingrid Dreveny, and Hajime Niwa for fruitful discussions, Suhail Islam for helping with the graphics. T.H. wishes to thank E. Dodson and G. Murshadov of University of York for helpful discussions. T.H. was funded by Cancer Research UK. J.M. acknowledges financial support from the Robert A. Welch Foundation (Q-1512), the American Heart Association (AHA-TX0160107Y), the National Institute of Health (R01-GM067801), and a National Science Foundation Career Award (MCB-0237796). J.M. received the Award for Distinguished Young Scholars Abroad from the National Natural Science Foundation of China. X.Z. and P.F. wish to thank the Wellcome Trust for their generous funding.

PY - 2003/12

Y1 - 2003/12

N2 - p97/VCP is a member of the AAA ATPase family and has roles in both membrane fusion and ubiquitin dependent protein degradation. Here, we present a 3.6Å crystal structure of murine p97 in which D2 domain has been modelled as poly-alanine and the remaining ~100 residues are absent. The resulting structure illustrates a head-to-tail packing arrangement of the two p97 AAA domains in a natural hexameric state with D1 ADP bound and D2 nucleotide free. The head-to-tail packing arrangement observed in this structure is in contrast to our previously predicted tail-to-tail packing model. The linker between the D1 and D2 domains is partially disordered, suggesting a flexible nature. Normal mode analysis of the crystal structure suggests anti-correlated motions and distinct conformational states of the two AAA domains.

AB - p97/VCP is a member of the AAA ATPase family and has roles in both membrane fusion and ubiquitin dependent protein degradation. Here, we present a 3.6Å crystal structure of murine p97 in which D2 domain has been modelled as poly-alanine and the remaining ~100 residues are absent. The resulting structure illustrates a head-to-tail packing arrangement of the two p97 AAA domains in a natural hexameric state with D1 ADP bound and D2 nucleotide free. The head-to-tail packing arrangement observed in this structure is in contrast to our previously predicted tail-to-tail packing model. The linker between the D1 and D2 domains is partially disordered, suggesting a flexible nature. Normal mode analysis of the crystal structure suggests anti-correlated motions and distinct conformational states of the two AAA domains.

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The crystal structure of murine p97/VCP at 3.6 Å

Abstract

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