PXD056334

PXD056334 is an original dataset announced via ProteomeXchange.

Title	Molecular mechanism of ssDNA-mediated allosteric activation of the WYL-domain containing transcription regulator, DriD
Description	WYL domain containing transcription factors play critical roles in regulating fundamental processes in bacterial physiology. The Caulobacter crescentus DriD protein is a WYL transcription regulator recently shown to activate a DNA damage response pathway that is independent of the major bacterial SOS repair system. DriD is a 327-residue homodimer and contains a unique fold composed of a N-terminal winged helix-turn-helix DNA binding domain (DNABD), linker region, three-helix bundle (3HB), WYL domain, and WYL C-terminal extension (WCX) dimerization domain. DriD binds ssDNA, which acts as a genotoxic signal that accumulates during double stranded DNA breaks, within its WYL domain. This interaction activates target DNA binding by DriD. However, the molecular mechanism by which ssDNA binding to the WYL domain, which is ~50 Å from the DNABD, activates DriD is unknown. Here, we describe structural and biochemical studies that indicate a novel allosteric mechanism of DriD activation. These data indicate that there is an inhibitory interaction formed between the DNABD and 3HB in the apo form, which is freed upon ssDNA binding. DriD represents the largest class of WYL regulator and thus can serve as a model for understanding activation by WYL activators including those in pathogenic bacteria.
HostingRepository	PRIDE
AnnounceDate	2025-04-14
AnnouncementXML	Submission_2025-04-14_10:26:27.119.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Thomas Wales
SpeciesList	scientific name: Caulobacter phage CcrColossus; NCBI TaxID: 1211640;
ModificationList	No PTMs are included in the dataset
Instrument	Synapt MS

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-27 11:52:25	ID requested
⏵ 1	2025-04-14 10:26:27	announced

Dataset with its publication pending

submitter keyword: DriD

transcription regulator HDX-MS

WYL domain

hydrogen/deuterium exchange mass spectrometry

Thomas E. Wales
contact affiliation	Northeastern University
contact email	t.wales@northeastern.edu
lab head
Thomas Wales
contact affiliation	Northeastern University
contact email	t.wales@northeastern.edu
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/2025/04/PXD056334

PRIDE project URI

• PRIDE
  1. PXD056334
     1. Label: PRIDE project
     2. Name: Molecular mechanism of ssDNA-mediated allosteric activation of the WYL-domain containing transcription regulator, DriD