PXD017406

PXD017406 is an original dataset announced via ProteomeXchange.

Title	HX-MS data: Feedback regulation of heat shock factor 1 (Hsf1) activity by Hsp70-mediated trimer unzipping and dissociation from DNA
Description	The heat shock response is a universal transcriptional response to proteotoxic stress orchestrated by heat shock transcription factor Hsf1 in all eukaryotic cells. Despite over 40 years of intense research, the mechanism of HSF1 activity regulation remains poorly understood at a molecular level. In metazoa Hsf1 trimerizes upon heat shock through a leucin-zipper domain and binds to DNA. How Hsf1 is dislodged from DNA and monomerized remained enigmatic. Here, using purified proteins we demonstrate that unmodified trimeric Hsf1 is dissociated from DNA in vitro by Hsc70 and DnaJB1. Hsc70 binds to multiple sites in Hsf1 with different affinities. Hsf1 trimers are monomerized by successive cycles of entropic pulling, unzipping the triple leucinezipper. Starting this unzipping at several protomers of the Hsf1 trimer results in faster monomerization. This process directly monitors the concentration of Hsc70 and DnaJB1. During heat shock adaptation Hsc70 first binds to a high affinity site in the transactivation domain leading to partial attenuation of the response and subsequently, at higher concentrations, Hsc70 removes Hsf1 from DNA to restore the resting state.
HostingRepository	PRIDE
AnnounceDate	2020-06-22
AnnouncementXML	Submission_2020-06-21_16:21:51.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Szymon Kmiecik
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	maXis

Revision	Datetime	Status	ChangeLog Entry
0	2020-02-05 07:07:26	ID requested
⏵ 1	2020-06-21 16:21:52	announced

Kmiecik SW, Le Breton L, Mayer MP, Feedback regulation of heat shock factor 1 (Hsf1) activity by Hsp70-mediated trimer unzipping and dissociation from DNA. EMBO J, 39(14):e104096(2020) [pubmed]

submitter keyword: Heat shock response, heat shock factor, Hsf1, Hsp70, DnaJB1/Hdj1, attenuation, DNA binding, entropic pulling

Matthias Peter Mayer
contact affiliation	Center for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBHAlliance, Im Neuenheimer Feld 282, D-69120 Heidelberg, Germany
contact email	m.mayer@zmbh.uni-heidelberg.de
lab head
Szymon Kmiecik
contact affiliation	Center for Molecular Biology of Heidelberg University (ZMBH)
contact email	s.kmiecik@zmbh.uni-heidelberg.de
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/2020/06/PXD017406

PRIDE project URI

• PRIDE
  1. PXD017406
     1. Label: PRIDE project
     2. Name: HX-MS data: Feedback regulation of heat shock factor 1 (Hsf1) activity by Hsp70-mediated trimer unzipping and dissociation from DNA