Conformational changes in the AAA ATPase p97-p47 adaptor complex

Fabienne Beuron, Ingrid Dreveny, Xuemei Yuan, Valerie E. Pye, Ciaran Mckeown, Louise C. Briggs, Matthew J. Cliff, Yayoi Kaneko, Russell Wallis, Rivka L. Isaacson, John E. Ladbury, Steve J. Matthews, Hisao Kondo, Xiaodong Zhang, Paul S. Freemont

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80 Citations (Scopus)

Abstract

The AAA + ATPase p97/VCP, helped by adaptor proteins, exerts its essential role in cellular events such as endoplasmic reticulum-associated protein degradation or the reassembly of Golgi, ER and the nuclear envelope after mitosis. Here, we report the three-dimensional cryo-electron microscopy structures at ∼20 Å resolution in two nucleotide states of the endogenous hexameric p97 in complex with a recombinant p47 trimer, one of the major p97 adaptor proteins involved in membrane fusion. Depending on the nucleotide state, we observe the p47 trimer to be in two distinct arrangements on top of the p97 hexamer. By combining the EM data with NMR and other biophysical measurements, we propose a model of ATP-dependent p97(N) domain motions that lead to a rearrangement of p47 domains, which could result in the disassembly of target protein complexes.

Original languageEnglish
Pages (from-to)1967-1976
Number of pages10
JournalEMBO Journal
Volume25
Issue number9
DOIs
Publication statusPublished - May 3 2006
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Beuron, F., Dreveny, I., Yuan, X., Pye, V. E., Mckeown, C., Briggs, L. C., Cliff, M. J., Kaneko, Y., Wallis, R., Isaacson, R. L., Ladbury, J. E., Matthews, S. J., Kondo, H., Zhang, X., & Freemont, P. S. (2006). Conformational changes in the AAA ATPase p97-p47 adaptor complex. EMBO Journal, 25(9), 1967-1976. https://doi.org/10.1038/sj.emboj.7601055