Structural basis for active single and double ring complexes in human mitochondrial Hsp60-Hsp10 chaperonin

Yacob Gomez-Llorente, Fady Jebara, Malay Patra, Radhika Malik, Shahar Nisemblat, Orna Chomsky-Hecht, Avital Parnas, Abdussalam Azem, Joel A. Hirsch, Iban Ubarretxena-Belandia*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

mHsp60-mHsp10 assists the folding of mitochondrial matrix proteins without the negative ATP binding inter-ring cooperativity of GroEL-GroES. Here we report the crystal structure of an ATP (ADP:BeF3-bound) ground-state mimic double-ring mHsp6014-(mHsp107)2 football complex, and the cryo-EM structures of the ADP-bound successor mHsp6014-(mHsp107)2 complex, and a single-ring mHsp607-mHsp107 half-football. The structures explain the nucleotide dependence of mHsp60 ring formation, and reveal an inter-ring nucleotide symmetry consistent with the absence of negative cooperativity. In the ground-state a two-fold symmetric H-bond and a salt bridge stitch the double-rings together, whereas only the H-bond remains as the equatorial gap increases in an ADP football poised to split into half-footballs. Refolding assays demonstrate obligate single- and double-ring mHsp60 variants are active, and complementation analysis in bacteria shows the single-ring variant is as efficient as wild-type mHsp60. Our work provides a structural basis for active single- and double-ring complexes coexisting in the mHsp60-mHsp10 chaperonin reaction cycle.

Original languageEnglish
Article number1916
JournalNature Communications
Volume11
Issue number1
DOIs
StatePublished - 1 Dec 2020

Funding

FundersFunder number
Basque Excellence Research Centre
Fundación Biofísica Bizkaia
Icahn School of Medicine
National Institutes of Health1S10RR026473
National Institute of General Medical SciencesP41GM103310
Simons FoundationSF349247
Agouron InstituteOD019994, F00316
Empire State Development's Division of Science, Technology and Innovation
United States-Israel Binational Science Foundation2015214
Council for Higher Education

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