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Four-colour FRET reveals directionality in the Hsp90 multicomponent machinery

Author

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  • C. Ratzke

    (Technische Universität München
    Present address: Department of Physics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA)

  • B. Hellenkamp

    (Technische Universität München)

  • T. Hugel

    (Technische Universität München)

Abstract

In living organisms, most proteins work in complexes to form multicomponent protein machines. The function of such multicomponent machines is usually addressed by dividing them into a collection of two state systems at equilibrium. Many molecular machines, like Hsp90, work far from equilibrium by utilizing the energy of ATP hydrolysis. In these cases, important information is gained from the observation of the succession of more than two states in a row. We developed a four-colour single-molecule FRET system to observe the succession of states in the heat shock protein 90 (Hsp90) system, consisting of an Hsp90 dimer, the cochaperone p23 and nucleotides. We show that this multicomponent system is a directional ATP-dependent machinery. This reveals a previously undescribed mechanism on how cochaperones can modify Hsp90, namely by strengthening of the coupling between ATP hydrolysis and a kinetic step involved in the Hsp90 system resulting in a stronger directionality.

Suggested Citation

  • C. Ratzke & B. Hellenkamp & T. Hugel, 2014. "Four-colour FRET reveals directionality in the Hsp90 multicomponent machinery," Nature Communications, Nature, vol. 5(1), pages 1-9, September.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5192
    DOI: 10.1038/ncomms5192
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    Cited by:

    1. Leonie Vollmar & Julia Schimpf & Bianca Hermann & Thorsten Hugel, 2024. "Cochaperones convey the energy of ATP hydrolysis for directional action of Hsp90," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    2. Paul David Harris & Alessandra Narducci & Christian Gebhardt & Thorben Cordes & Shimon Weiss & Eitan Lerner, 2022. "Multi-parameter photon-by-photon hidden Markov modeling," Nature Communications, Nature, vol. 13(1), pages 1-12, December.

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