PXD010069-1

PXD010069 is an original dataset announced via ProteomeXchange.

Title	Hsp70 ATP-dependent dimerization and Chaperone/Co-chaperone Interactions
Description	Eukaryotic protein homeostasis (proteostasis) is largely dependent on the action of highly conserved Hsp70 molecular chaperones. Recent evidence indicates that apart from conserved molecular allostery, Hsp70 proteins retained and adapted throughout the evolution the ability to assemble as functionally relevant ATP-bound dimers. Here we have compared the ATP-dependent dimerization of DnaK, human stress-inducible Hsp70, Hsc70 and BiP Hsp70 proteins showing that their dimerization propensities differ with stress-inducible Hsp70 being predominantly dimeric in the presence of ATP. The structural analyses using hydrogen/deuterium exchange mass spectrometry, native electrospray ionization mass spectrometry, chemical cross-linking and small-angle X-ray scattering revealed that stress-inducible Hsp70 assembles in solution as an antiparallel dimer with the intermolecular interface closely resembling the ATP-bound dimer interfaces captured in DnaK and BiP crystal structures. ATP-dependent dimerization of stress-inducible Hsp70 is necessary for its efficient interaction with Hsp40 as shown by experiments with dimerization-deficient mutants. Moreover, dimerization of ATP-bound Hsp70 is required for its participation in high molecular weight protein complexes detected ex vivo supporting its functional role in vivo. As human cytosolic Hsp70 has the ability to interact with tetratricopeptide repeat (TPR) domain containing co-chaperones, we tested the interaction of Hsp70 ATP-dependent dimer with Chip and Tomm34 co-chaperones. While Chip associates with intact Hsp70 dimer to form a larger complex, binding of Tomm34 disrupts Hsp70 dimer and this event plays an important role in Hsp70 activity regulation. In summary, this study provides structural evidence of robust ATP-dependent antiparallel dimerization of human inducible Hsp70 protein and suggests novel role of TPR domain co-chaperones in multichaperone complexes involving Hsp70 ATP-bound dimers.
HostingRepository	PRIDE
AnnounceDate	2018-12-11
AnnouncementXML	Submission_2018-12-11_06:15:50.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Petr Man
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	solariX

Revision	Datetime	Status	ChangeLog Entry
0	2018-06-08 02:09:01	ID requested
⏵ 1	2018-12-11 06:15:52	announced
2	2024-10-22 04:45:50	announced	2024-10-22: Updated project metadata.

Trcka F, Durech M, Vankova P, Chmelik J, Martinkova V, Hausner J, Kadek A, Marcoux J, Klumpler T, Vojtesek B, Muller P, Man P, Human Stress-inducible Hsp70 Has a High Propensity to Form ATP-dependent Antiparallel Dimers That Are Differentially Regulated by Cochaperone Binding. Mol Cell Proteomics, 18(2):320-337(2019) [pubmed]

submitter keyword: Hsp70, co-chaperone, Chip, Tomm34, dimer

Petr Man
contact affiliation	Institute of Microbiology of the CAS, Czech Republic
contact email	pman@biomed.cas.cz
lab head
Petr Man
contact affiliation	Institute of Microbiology of the CAS
contact email	pman@biomed.cas.cz
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD010069
     1. Label: PRIDE project
     2. Name: Hsp70 ATP-dependent dimerization and Chaperone/Co-chaperone Interactions