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  • The EMBO Journal (2006) 25, 1967 - 1976
  • doi:10.1038/sj.emboj.7601055

Published online: 6 April 2006

Conformational changes in the AAA ATPase p97–p47 adaptor complex

Fabienne Beuron1, Ingrid Dreveny1, Xuemei Yuan1, Valerie E Pye1, Ciaran Mckeown1, Louise C Briggs1, Matthew J Cliff2, Yayoi Kaneko3,4, Russell Wallis5,6, Rivka L Isaacson1, John E Ladbury2, Steve J Matthews1, Hisao Kondo3,4, Xiaodong Zhang1 and Paul S Freemont1

  1. Centre for Structural Biology, Division of Molecular Biosciences, Imperial College London, South Kensington, London, UK
  2. Department of Biochemistry and Molecular Biology, University College London, London, UK
  3. Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK
  4. PRESTO and SORST, Japan Science and Technology Corporation, Japan
  5. Department of Biochemistry, University of Oxford, Oxford, UK
  6. Department of Infection, Immunity, and Inflammation, Medical Research Council Immunochemistry Unit, University of Leicester, Leicester, UK

Correspondence to:

Paul S Freemont, Centre for Structural Biology, Division of Molecular Biosciences, Imperial College London, South Kensington Campus, Biochemistry Building, South Kensington, London SW7 2AZ, UK. Tel.: +44 20 7594 5327; Fax: +44 20 7594 3057; E-mail: p.freemont@imperial.ac.uk

Received 14 December 2005; Accepted 27 February 2006

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 approx20 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.

  • Keywords:

    • AAA ATPase,
    • conformational change,
    • Cryo-EM,
    • p47,
    • p97