PXD031315 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | The structural basis of Cdc7-Dbf4 kinase dependent targeting and phosphorylation of the MCM2-7 double hexamer |
Description | The 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. |
HostingRepository | PRIDE |
AnnounceDate | 2023-11-14 |
AnnouncementXML | Submission_2023-11-14_08:54:39.743.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Alex Montoya |
SpeciesList | scientific name: Saccharomyces cerevisiae; NCBI TaxID: NCBITaxon:4932; scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932; |
ModificationList | thiophosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Q Exactive HF-X |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-01-30 10:39:17 | ID requested | |
1 | 2022-05-31 05:33:41 | announced | |
⏵ 2 | 2023-11-14 08:54:40 | announced | 2023-11-14: 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 affiliation | Core facility head |
contact email | p.shliaha@lms.mrc.ac.uk |
lab head | |
Alex Montoya |
contact affiliation | Medical Research Council - London Institute of Medical Sciences |
contact email | alex.montoya@lms.mrc.ac.uk |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD031315
- Label: PRIDE project
- Name: The structural basis of Cdc7-Dbf4 kinase dependent targeting and phosphorylation of the MCM2-7 double hexamer