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

Autor:	Teixeira F; Department of Molecular, Cellular and Developmental, University of Michigan, Ann Arbor, 48109-1085, MI, USA.; i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, 4200-135, Portugal.; IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, 4050-313, Portugal.; ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, 4050-313, Portugal., Tse E; Department of Biochemistry and Biophysics, Institute for Neurodegenerative Diseases, University of California, San Francisco, 94158, CA, USA., Castro H; i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, 4200-135, Portugal.; IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, 4050-313, Portugal., Makepeace KAT; Department of Biochemistry and Microbiology, University of Victoria, Victoria, V8P 5C2, BC, Canada.; Genome British Columbia Proteomics Centre, University of Victoria, Victoria, V8Z 7X8, BC, Canada., Meinen BA; Department of Molecular, Cellular and Developmental, University of Michigan, Ann Arbor, 48109-1085, MI, USA.; Howard Hughes Medical Institute, Ann Arbor, 48109-1085, MI, USA., Borchers CH; Department of Biochemistry and Microbiology, University of Victoria, Victoria, V8P 5C2, BC, Canada.; Genome British Columbia Proteomics Centre, University of Victoria, Victoria, V8Z 7X8, BC, Canada.; Gerald Bronfman Department of Oncology, Jewish General Hospital, Montreal, H4A 3T2, QC, Canada.; Proteomics Centre, Segal Cancer Centre, Lady Davis Institute, Jewish General Hospital, Montreal, H3T 1E2, QC, Canada., Poole LB; Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, 27157, NC, USA., Bardwell JC; Department of Molecular, Cellular and Developmental, University of Michigan, Ann Arbor, 48109-1085, MI, USA.; Howard Hughes Medical Institute, Ann Arbor, 48109-1085, MI, USA., Tomás AM; i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, 4200-135, Portugal.; IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, 4050-313, Portugal.; ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, 4050-313, Portugal., Southworth DR; Department of Biochemistry and Biophysics, Institute for Neurodegenerative Diseases, University of California, San Francisco, 94158, CA, USA. daniel.southworth@ucsf.edu., Jakob U; Department of Molecular, Cellular and Developmental, University of Michigan, Ann Arbor, 48109-1085, MI, USA. ujakob@umich.edu.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2019 Feb 08; Vol. 10 (1), pp. 659. Date of Electronic Publication: 2019 Feb 08.
DOI:	10.1038/s41467-019-08565-8
Abstrakt:	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.
Databáze:	MEDLINE
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