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PXD009503

PXD009503 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleTargeting G protein-coupled receptor signaling at the G protein level with a selective nanobody inhibitor
DescriptionG protein-coupled receptors (GPCRs) activate heterotrimeric G proteins by mediating a GDP to GTP exchange in the Gα subunit. This leads to dissociation of the heterotrimer into Gα-GTP and Gβγ dimer. The Gα-GTP and Gβγ dimer each regulate a variety of downstream pathways to control various aspects of human physiology. Dysregulated Gβγ-signaling is a central element of various neurological and cancer-related anomalies. However, Gβγ also serves as a negative regulator of Gα that is essential for G protein inactivation, and thus has the potential for numerous side effects when targeted therapeutically. Here we report a llama-derived nanobody (Nb5) that binds tightly to the Gβγ dimer. Nb5 responds to all combinations of β- and γ-subtypes and competes with other Gβγ-regulatory proteins for a common binding site on the Gβγ dimer. Despite its inhibitory effect on Gβγ-mediated signaling, Nb5 has no effect on GTP-bound Gαq and Gαs-mediated signaling events in the environment of a living cell.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_04:44:34.244.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterSahil Gulati
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListphosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentLTQ Orbitrap
Dataset History
RevisionDatetimeStatusChangeLog Entry
02018-04-16 01:36:56ID requested
12018-10-19 11:31:38announced
22024-10-22 04:44:42announced2024-10-22: Updated project metadata.
Publication List
10.1038/s41467-018-04432-0;
Gulati S, Jin H, Masuho I, Orban T, Cai Y, Pardon E, Martemyanov KA, Kiser PD, Stewart PL, Ford CP, Steyaert J, Palczewski K, Targeting G protein-coupled receptor signaling at the G protein level with a selective nanobody inhibitor. Nat Commun, 9(1):1996(2018) [pubmed]
Keyword List
curator keyword: Biomedical
submitter keyword: LC-MS
Contact List
Krzysztof Palczewski
contact affiliationDepartment of Pharmacology, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA
contact emailkxp65@case.edu
lab head
Sahil Gulati
contact affiliationCase Western Reserve University
contact emails.gulati@case.edu
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
Repository Record List
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