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iScience. 2020 Dec 31;24(1):102022. doi: 10.1016/j.isci.2020.102022. eCollection 2021 Jan 22.

Cryo-EM structure of human mitochondrial HSPD1.

iScience

David P Klebl, Matthew C Feasey, Emma L Hesketh, Neil A Ranson, Heiko Wurdak, Frank Sobott, Robin S Bon, Stephen P Muench

Affiliations

  1. School of Biomedical Sciences, Faculty of Biological Sciences & Astbury Centre for Structural and Molecular Biology, University of Leeds, Leeds LS2 9JT, UK.
  2. School of Molecular and Cellular Biology, Faculty of Biological Sciences & Astbury Centre for Structural and Molecular Biology, University of Leeds, Leeds LS2 9JT, UK.
  3. School of Medicine, Faculty of Medicine and Health, Stem Cell and Brain Tumour Group, University of Leeds, Leeds LS9 7TF, UK.
  4. Department of Chemistry, Biomolecular & Analytical Mass Spectrometry Group, University of Antwerp, Antwerp, Belgium.
  5. School of Medicine, Faculty of Medicine and Health & Astbury Centre for Structural and Molecular Biology, University of Leeds, LS2 9JT Leeds, UK.

PMID: 33506187 PMCID: PMC7814154 DOI: 10.1016/j.isci.2020.102022

Abstract

Chaperonins play an important role in folding newly synthesized or translocated proteins in all organisms. The bacterial chaperonin GroEL has served as a model system for the understanding of these proteins. In comparison, its human homolog, known as mitochondrial heat shock protein family member D1 (HSPD1) is poorly understood. Here, we present the structure of HSPD1 in the apo state determined by cryo-electron microscopy (cryo-EM). Unlike GroEL, HSPD1 forms mostly single ring assemblies in the absence of co-chaperonin (HSPE1). Comparison with GroEL shows a rotation and increased flexibility of the apical domain. Together with published structures of the HSPD1/HSPE1 co-chaperonin complex, this work gives insight into the structural changes that occur during the catalytic cycle. This new understanding of HSPD1 structure and its rearrangements upon complex formation may provide new insights for the development of HSPD1-targeting treatments against a diverse range of diseases including glioblastoma.

© 2020.

Keywords: Molecular Biology; Molecular Structure

Conflict of interest statement

The authors declare no conflicts of interest.

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