PXD054414

PXD054414 is an original dataset announced via ProteomeXchange.

Title	Targeting Ras-, Rho-, and Rab-Family GTPases via a Conserved Cryptic Pocket
Description	The 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.
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-06_23:03:04.873.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Zhi Lin
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	6220 Time-of-Flight LC/MS

Revision	Datetime	Status	ChangeLog Entry
0	2024-07-30 17:38:26	ID requested
⏵ 1	2025-05-06 23:03:05	announced

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;

submitter keyword: GTPase

Johannes Morstein
contact affiliation	UCSF
contact email	johannes.morstein@ucsf.edu
lab head
Zhi Lin
contact affiliation	UCSF
contact email	zhi.lin@ucsf.edu
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/2025/05/PXD054414

PRIDE project URI

• PRIDE
  1. PXD054414
     1. Label: PRIDE project
     2. Name: Targeting Ras-, Rho-, and Rab-Family GTPases via a Conserved Cryptic Pocket