Structural highlights
Function
[GBB1_BOVIN] Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction. [GBG1_BOVIN] Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction.
Publication Abstract from PubMed
G protein-coupled receptors (GPCRs) activate heterotrimeric G proteins by mediating a GDP to GTP exchange in the Galpha subunit. This leads to dissociation of the heterotrimer into Galpha-GTP and Gbetagamma dimer. The Galpha-GTP and Gbetagamma dimer each regulate a variety of downstream pathways to control various aspects of human physiology. Dysregulated Gbetagamma-signaling is a central element of various neurological and cancer-related anomalies. However, Gbetagamma also serves as a negative regulator of Galpha 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 Gbetagamma dimer. Nb5 responds to all combinations of beta-subtypes and gamma-subtypes and competes with other Gbetagamma-regulatory proteins for a common binding site on the Gbetagamma dimer. Despite its inhibitory effect on Gbetagamma-mediated signaling, Nb5 has no effect on Galphaq-mediated and Galphas-mediated signaling events in living cells.
Targeting G protein-coupled receptor signaling at the G protein level with a selective nanobody inhibitor.,Gulati S, Jin H, Masuho I, Orban T, Cai Y, Pardon E, Martemyanov KA, Kiser PD, Stewart PL, Ford CP, Steyaert J, Palczewski K Nat Commun. 2018 May 18;9(1):1996. doi: 10.1038/s41467-018-04432-0. PMID:29777099[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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. 2018 May 18;9(1):1996. doi: 10.1038/s41467-018-04432-0. PMID:29777099 doi:http://dx.doi.org/10.1038/s41467-018-04432-0
