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PXD031315-2

PXD031315 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleThe structural basis of Cdc7-Dbf4 kinase dependent targeting and phosphorylation of the MCM2-7 double hexamer
DescriptionThe controlled assembly of replication forks is critical for genome stability. The Dbf4-dependent Cdc7 kinase (DDK) initiates replisome assembly by phosphorylating the MCM2-7 replicative helicase at the N-terminal tails of Mcm2, Mcm4 and Mcm6. At present, it remains poorly understood how DDK docks onto the helicase and how the kinase targets distal Mcm subunits for phosphorylation. By cryo-electron microscopy and biochemical analysis we discovered that an interaction between the HBRCT domain of Dbf4 with Mcm2 serves as an anchoring point, which supports binding of DDK across the MCM2-7 double-hexamer interface and phosphorylation of Mcm4 on the opposite hexamer. Moreover, a rotation of DDK along its anchoring point allows phosphorylation of Mcm2 and Mcm6 on opposite hexamers. In summary, our work provides fundamental insights in the DDK structure, control and the selective activation of the MCM2-7 helicase during DNA replication, which can be exploited for development of novel DDK inhibitors.
HostingRepositoryPRIDE
AnnounceDate2023-11-14
AnnouncementXMLSubmission_2023-11-14_08:54:39.743.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterAlex Montoya
SpeciesList scientific name: Saccharomyces cerevisiae; NCBI TaxID: NCBITaxon:4932; scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932;
ModificationListthiophosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive HF-X
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-01-30 10:39:17ID requested
12022-05-31 05:33:41announced
22023-11-14 08:54:40announced2023-11-14: Updated project metadata.
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: cryo-EM, DDK, yeast, S-phase, Dbf4, molecular dynamics, helicase, origins, Cdc7, helicase activation, kinase,MCM2-7, DNA replication
Contact List
Dr Pavel Shliaha
contact affiliationCore facility head
contact emailp.shliaha@lms.mrc.ac.uk
lab head
Alex Montoya
contact affiliationMedical Research Council - London Institute of Medical Sciences
contact emailalex.montoya@lms.mrc.ac.uk
dataset submitter
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Dataset FTP location
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