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PXD054414

PXD054414 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleTargeting Ras-, Rho-, and Rab-Family GTPases via a Conserved Cryptic Pocket
DescriptionThe family of Ras-like GTPases consists of over 150 different members, regulated by an even larger number of guanine exchange factors (GEFs) and GTPase-activating proteins (GAPs) which comprise cellular switch networks that govern cell motility, growth, polarity, protein trafficking, and gene expression. Efforts to develop selective small molecule probes and drugs for these proteins have been hampered by the high affinity of GTP and lack of allosteric regulatory sites. This paradigm was recently challenged by the discovery of a cryptic allosteric pocket in the Switch II region of K-Ras. Here we ask if similar pockets are present in GTPases beyond K-Ras. We systematically surveyed members of the Ras-, Rho-, and Rab-family of GTPases and found that many GTPases exhibit targetable Switch II pockets. Notable differences in the composition and conservation of key residues offer potential for the development of optimized inhibitors for many members of this previously undruggable family.
HostingRepositoryPRIDE
AnnounceDate2025-05-07
AnnouncementXMLSubmission_2025-05-06_23:03:04.873.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterZhi Lin
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListacetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument6220 Time-of-Flight LC/MS
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-07-30 17:38:26ID requested
12025-05-06 23:03:05announced
Publication List
Morstein J, Bowcut V, Fernando M, Yang Y, Zhu L, Jenkins ML, Evans JT, Guiley KZ, Peacock DM, Krahnke S, Lin Z, Taran KA, Huang BJ, Stephen AG, Burke JE, Lightstone FC, Shokat KM, Targeting Ras-, Rho-, and Rab-family GTPases via a conserved cryptic pocket. Cell, 187(22):6379-6392.e17(2024) [pubmed]
10.1016/j.cell.2024.08.017;
Keyword List
submitter keyword: GTPase
Contact List
Johannes Morstein
contact affiliationUCSF
contact emailjohannes.morstein@ucsf.edu
lab head
Zhi Lin
contact affiliationUCSF
contact emailzhi.lin@ucsf.edu
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
Repository Record List
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