PXD074705

PXD074705 is an original dataset announced via ProteomeXchange.

Title	Structures reveal DnaA domain I dimer conserved across Actinomycetes: implications for replication initiation
Description	DNA replication is a fundamental process in biology with initiation marking its key, first step. In bacteria, DNA replication is initiated by the DnaA protein. DnaA exhibits multidomain architecture, consisting of an N-terminal domain I, linker region, AAA+ family ATPase cassette, and C-terminal DNA-binding motif. Taxon-specific regulatory functions are primarily coordinated by the DnaA domain I, which exhibits substantial sequence variation across bacteria. Notably, although the DnaA domain I has been shown to be essential, its contributions to initiation are not completely understood. Importantly, studies have indicated a role for DnaA domain I dimerization in the cooperative assembly of the initiation complex at the origin. However, the mechanism(s) and molecular basis of DnaA domain I dimerization have proved elusive. Here, we report structures of the DnaA domain I from ten Actinobacterial species. Strikingly, all structures reveal the same, unique dimer, and key elements which support DnaA domain I self-interaction are broadly conserved across the class Actinomycetes. Further, a suite of biochemical oligomerization assays and HDX-MS studies support the structural dimer. These findings suggest weak dimerization, as mediated by the DnaA domain I, acts a fine-tuned trigger in cooperative oriC assembly and that this is a broadly conserved biological mechanism for replication initiation in the class Actinomycetes.
HostingRepository	PRIDE
AnnounceDate	2026-05-27
AnnouncementXML	Submission_2026-05-27_11:05:47.831.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Thomas Wales
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Synapt MS

Revision	Datetime	Status	ChangeLog Entry
0	2026-02-20 20:32:12	ID requested
⏵ 1	2026-05-27 11:05:48	announced

Dataset with its publication pending

submitter keyword: HDX MS

DnaA

Dimerization

DNA replication

Dimeric interface

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

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PRIDE project URI

• PRIDE
  1. PXD074705
     1. Label: PRIDE project
     2. Name: Structures reveal DnaA domain I dimer conserved across Actinomycetes: implications for replication initiation