PXD010281

PXD010281 is an original dataset announced via ProteomeXchange.

Title	Chaperone Activation and Client Binding of a 2-Cysteine Peroxiredoxin
Description	Many 2-Cys-peroxiredoxins (2-Cys-Prxs) serve as dual-function proteins. Active as peroxidases under non-stress conditions, they convert into effective chaperones under stress conditions. While their peroxidase activity has been extensively studied and shown to involve cycles of redox-mediated oligomeric changes, the mechanisms by which 2-Cys-Prxs sense stress and convert into general chaperones remain to be defined. Here we focus on the Leishmania infantum mitochondrial 2-Cys-Prx (mTXNPx, Prx1m), which, in its reduced, decameric form, readily adopts chaperone function upon exposure to heat shock temperatures. This activity is crucial for parasite survival in mammalian hosts. Here we have determined the cryo-EM structure of mTXNPx in complex with a thermally unfolded client protein that identifies the flexible N-termini of mTXNPx to form a well-resolved central belt that contacts and encapsulates the unstructured client protein in the center of the decamer ring. In vivo cross-linking studies combined with quantitative in vitro cross-linking experiments further support these interactions, and demonstrate that mTXNPx decamers undergo substantial temperature-dependent structural rearrangements specifically at the dimer-dimer interfaces. These structural changes appear crucial for exposing chaperone client binding sites that are otherwise buried in the peroxidase-active protein. Based on this mechanism, we propose that mTXNPx is the founding member of heat-stress activated chaperones in parasitic mitochondria that facilitate the transition to warm-blooded host environments.
HostingRepository	PRIDE
AnnounceDate	2019-02-19
AnnouncementXML	Submission_2019-02-19_07:54:09.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Karl Makepeace
SpeciesList	scientific name: Photinus pyralis (Common eastern firefly) (Lampyris pyralis); NCBI TaxID: 7054; scientific name: Leishmania infantum; NCBI TaxID: 5671;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2018-07-02 01:55:11	ID requested
⏵ 1	2019-02-19 07:54:11	announced

Teixeira F, Tse E, Castro H, Makepeace KAT, Meinen BA, Borchers CH, Poole LB, Bardwell JC, Tom, á, s AM, Southworth DR, Jakob U, Chaperone activation and client binding of a 2-cysteine peroxiredoxin. Nat Commun, 10(1):659(2019) [pubmed]

curator keyword: Biological

submitter keyword: cross-linking

chaperone activation

chaperone-client complex

Christoph H. Borchers
contact affiliation	1. Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada; 2. University of Victoria Genome BC Proteomics Centre, University of Victoria, Victoria, British Columbia, Canada; 3. Gerald Bronfman Department of Oncology, Jewish General Hospital, Montreal, Quebec, Canada; 4. Segal Cancer Proteomics Centre, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, Quebec, Canada
contact email	christoph@proteincentre.com
lab head
Karl Makepeace
contact affiliation	University of Victoria
contact email	karlm@uvic.ca
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/02/PXD010281

PRIDE project URI

• PRIDE
  1. PXD010281
     1. Label: PRIDE project
     2. Name: Chaperone Activation and Client Binding of a 2-Cysteine Peroxiredoxin