PXD009503-2

PXD009503 is an original dataset announced via ProteomeXchange.

Title	Targeting G protein-coupled receptor signaling at the G protein level with a selective nanobody inhibitor
Description	G 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.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:44:34.244.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sahil Gulati
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2018-04-16 01:36:56	ID requested
1	2018-10-19 11:31:38	announced
⏵ 2	2024-10-22 04:44:42	announced	2024-10-22: Updated project metadata.

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]

curator keyword: Biomedical

submitter keyword: LC-MS

Krzysztof Palczewski
contact affiliation	Department of Pharmacology, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA
contact email	kxp65@case.edu
lab head
Sahil Gulati
contact affiliation	Case Western Reserve University
contact email	s.gulati@case.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/2018/10/PXD009503

PRIDE project URI

• PRIDE
  1. PXD009503
     1. Label: PRIDE project
     2. Name: Targeting G protein-coupled receptor signaling at the G protein level with a selective nanobody inhibitor