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  • The EMBO Journal (2008) 27, 2789 - 2798
  • doi:10.1038/emboj.2008.190

Published online: 25 September 2008

Structural and functional coupling of Hsp90- and Sgt1-centred multi-protein complexesEMBO Open

Minghao Zhang1, Marta Botër2, Kuoyu Li3, Yasuhiro Kadota4, Barry Panaretou3, Chrisostomos Prodromou1, Ken Shirasu2,4 and Laurence H Pearl1

  1. Section of Structural Biology, The Institute of Cancer Research, Chester Beatty Laboratories, London, UK
  2. Sainsbury Laboratory, John Innes Centre, Norwich, UK
  3. Chemical Biology Research Group, Pharmaceutical Science Division, King's College London, London, UK
  4. Plant Immunity Research Group, RIKEN Plant Science Center, Yokohama, Japan

Correspondence to:

Ken Shirasu, Plant Immunity Research Group, RIKEN Plant Science Center, 1-7-22 Suehiro-cho, Tsurumi, Yokohama 230-0045, Japan. Tel.: +81455039574; Fax: +81455039573; E-mail: ken.shirasu@psc.riken.jp

Laurence H Pearl, Section of Structural Biology, The Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK. Tel.: +44 207 970 6045/6; Fax: +44 207 970 6051; E-mail: laurence.pearl@icr.ac.uk

Received 30 April 2008; Accepted 2 August 2008

Sgt1 is an adaptor protein implicated in a variety of processes, including formation of the kinetochore complex in yeast, and regulation of innate immunity systems in plants and animals. Sgt1 has been found to associate with SCF E3 ubiquitin ligases, the CBF3 kinetochore complex, plant R proteins and related animal Nod-like receptors, and with the Hsp90 molecular chaperone. We have determined the crystal structure of the core Hsp90–Sgt1 complex, revealing a distinct site of interaction on the Hsp90 N-terminal domain. Using the structure, we developed mutations in Sgt1 interfacial residues, which specifically abrogate interaction with Hsp90, and disrupt Sgt1-dependent functions in vivo, in plants and yeast. We show that Sgt1 bridges the Hsp90 molecular chaperone system to the substrate-specific arm of SCF ubiquitin ligase complexes, suggesting a role in SCF assembly and regulation, and providing multiple complementary routes for ubiquitination of Hsp90 client proteins.

  • Keywords:

    • complex assembly,
    • crystal structure,
    • molecular chaperone,
    • protein–protein interactions,
    • ubiquitin ligase

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