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Nat Commun. 2019 Feb 8;10(1):659. doi: 10.1038/s41467-019-08565-8.

Chaperone activation and client binding of a 2-cysteine peroxiredoxin.

Author information

1
Department of Molecular, Cellular and Developmental, University of Michigan, Ann Arbor, 48109-1085, MI, USA.
2
i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, 4200-135, Portugal.
3
IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, 4050-313, Portugal.
4
ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, 4050-313, Portugal.
5
Department of Biochemistry and Biophysics, Institute for Neurodegenerative Diseases, University of California, San Francisco, 94158, CA, USA.
6
Department of Biochemistry and Microbiology, University of Victoria, Victoria, V8P 5C2, BC, Canada.
7
Genome British Columbia Proteomics Centre, University of Victoria, Victoria, V8Z 7X8, BC, Canada.
8
Howard Hughes Medical Institute, Ann Arbor, 48109-1085, MI, USA.
9
Gerald Bronfman Department of Oncology, Jewish General Hospital, Montreal, H4A 3T2, QC, Canada.
10
Proteomics Centre, Segal Cancer Centre, Lady Davis Institute, Jewish General Hospital, Montreal, H3T 1E2, QC, Canada.
11
Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, 27157, NC, USA.
12
Department of Biochemistry and Biophysics, Institute for Neurodegenerative Diseases, University of California, San Francisco, 94158, CA, USA. daniel.southworth@ucsf.edu.
13
Department of Molecular, Cellular and Developmental, University of Michigan, Ann Arbor, 48109-1085, MI, USA. ujakob@umich.edu.

Abstract

Many 2-Cys-peroxiredoxins (2-Cys-Prxs) are dual-function proteins, either acting as peroxidases under non-stress conditions or as chaperones during stress. The mechanism by which 2-Cys-Prxs switch functions remains to be defined. Our work focuses on Leishmania infantum mitochondrial 2-Cys-Prx, whose reduced, decameric subpopulation adopts chaperone function during heat shock, an activity that facilitates the transition from insects to warm-blooded host environments. Here, we have solved the cryo-EM structure of mTXNPx in complex with a thermally unfolded client protein, and revealed that the flexible N-termini of mTXNPx form a well-resolved central belt that contacts and encapsulates the unstructured client protein in the center of the decamer ring. In vivo and in vitro cross-linking studies provide further support for these interactions, and demonstrate that mTXNPx decamers undergo temperature-dependent structural rearrangements specifically at the dimer-dimer interfaces. These structural changes appear crucial for exposing chaperone-client binding sites that are buried in the peroxidase-active protein.

PMID:
30737390
PMCID:
PMC6368585
DOI:
10.1038/s41467-019-08565-8
[Indexed for MEDLINE]
Free PMC Article

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