| First Author | Gulati S | Year | 2018 |
| Journal | Nat Commun | Volume | 9 |
| Issue | 1 | Pages | 1996 |
| PubMed ID | 29777099 | Mgi Jnum | J:262914 |
| Mgi Id | MGI:6161033 | Doi | 10.1038/s41467-018-04432-0 |
| Citation | Gulati S, et al. (2018) Targeting G protein-coupled receptor signaling at the G protein level with a selective nanobody inhibitor. Nat Commun 9(1):1996 |
| abstractText | 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. |
