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PXD018910

PXD018910 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleStructure of the helicase core of Werner Helicase, a key target in microsatellite instability cancers
DescriptionLoss of WRN, a DNA repair helicase, was identified as a strong vulnerability of microsatellite instable(MSI) cancers, making WRN a promising drug target. We show that ATP binding and hydrolysis are required for genome integrity and viability of MSI cancer cells. We report a 2.2 Å crystal structure of the WRN helicase core (517-1093), comprising the two helicase subdomains and winged helix domain but not the HRDC domain or nuclease domains. The structure highlights unusual features: First, an atypical mode of nucleotide binding that results in unusual relative positioning of the two helicase subdomains. Second, an additional β-hairpin in the second helicase subdomain and an unusual helical hairpin in the Zn2+ binding domain. Modelling of the WRN helicase in complex with DNA suggests roles for these features in the binding of alternative DNA structures. NMR analysis of shows a weak interaction between the HRDC domain and the helicase core, indicating a possible biological role for this association. Together, this study will facilitate the structure-based development of inhibitors against WRN helicase.
HostingRepositoryPRIDE
AnnounceDate2020-11-11
AnnouncementXMLSubmission_2020-11-11_09:13:23.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterKlaus Rumpel
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentSynapt MS
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-04-29 15:04:16ID requested
12020-11-11 09:13:24announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Helicase, DNA binding, HDX, Deuterium Exchange
Contact List
Klaus Rumpel
contact affiliationDepartment of Cancer Cell Signaling, Boehringer Ingelheim Vienna
contact emailklaus.rumpel@boehringer-ingelheim.com
lab head
Klaus Rumpel
contact affiliationBoehringer Ingelheim RCV GmbH & Co KG
contact emailklaus.rumpel@boehringer-ingelheim.com
dataset submitter
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PRIDE project URI
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