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Protein unfolding as a switch from self-recognition to high-affinity client binding

Author

Listed:
  • Bastian Groitl

    (Cellular and Developmental Biology, University of Michigan)

  • Scott Horowitz

    (Cellular and Developmental Biology, University of Michigan
    Howard Hughes Medical Institute, University of Michigan)

  • Karl A. T. Makepeace

    (Genome BC Proteomics Centre, University of Victoria)

  • Evgeniy V. Petrotchenko

    (Genome BC Proteomics Centre, University of Victoria)

  • Christoph H. Borchers

    (Genome BC Proteomics Centre, University of Victoria)

  • Dana Reichmann

    (Cellular and Developmental Biology, University of Michigan
    Present address: Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Givat Ram Campus, Jerusalem 91904, Israel)

  • James C. A. Bardwell

    (Cellular and Developmental Biology, University of Michigan
    Howard Hughes Medical Institute, University of Michigan)

  • Ursula Jakob

    (Cellular and Developmental Biology, University of Michigan)

Abstract

Stress-specific activation of the chaperone Hsp33 requires the unfolding of a central linker region. This activation mechanism suggests an intriguing functional relationship between the chaperone’s own partial unfolding and its ability to bind other partially folded client proteins. However, identifying where Hsp33 binds its clients has remained a major gap in our understanding of Hsp33’s working mechanism. By using site-specific Fluorine-19 nuclear magnetic resonance experiments guided by in vivo crosslinking studies, we now reveal that the partial unfolding of Hsp33’s linker region facilitates client binding to an amphipathic docking surface on Hsp33. Furthermore, our results provide experimental evidence for the direct involvement of conditionally disordered regions in unfolded protein binding. The observed structural similarities between Hsp33’s own metastable linker region and client proteins present a possible model for how Hsp33 uses protein unfolding as a switch from self-recognition to high-affinity client binding.

Suggested Citation

  • Bastian Groitl & Scott Horowitz & Karl A. T. Makepeace & Evgeniy V. Petrotchenko & Christoph H. Borchers & Dana Reichmann & James C. A. Bardwell & Ursula Jakob, 2016. "Protein unfolding as a switch from self-recognition to high-affinity client binding," Nature Communications, Nature, vol. 7(1), pages 1-12, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10357
    DOI: 10.1038/ncomms10357
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