PXD018910-1

PXD018910 is an original dataset announced via ProteomeXchange.

Title	Structure of the helicase core of Werner Helicase, a key target in microsatellite instability cancers
Description	Loss 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.
HostingRepository	PRIDE
AnnounceDate	2020-11-11
AnnouncementXML	Submission_2020-11-11_09:13:23.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Klaus Rumpel
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Synapt MS

Revision	Datetime	Status	ChangeLog Entry
0	2020-04-29 15:04:16	ID requested
⏵ 1	2020-11-11 09:13:24	announced

Dataset with its publication pending

submitter keyword: Helicase, DNA binding, HDX, Deuterium Exchange

Klaus Rumpel
contact affiliation	Department of Cancer Cell Signaling, Boehringer Ingelheim Vienna
contact email	klaus.rumpel@boehringer-ingelheim.com
lab head
Klaus Rumpel
contact affiliation	Boehringer Ingelheim RCV GmbH & Co KG
contact email	klaus.rumpel@boehringer-ingelheim.com
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/2020/11/PXD018910

PRIDE project URI

• PRIDE
  1. PXD018910
     1. Label: PRIDE project
     2. Name: Structure of the helicase core of Werner Helicase, a key target in microsatellite instability cancers