期刊
NATURE COMMUNICATIONS
卷 9, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-018-04432-0
关键词
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资金
- National Institutes of Health [EY009339, EY027283, EY024864, DA35821, NS95809, P30EY011373, P30EY025585]
- Department of Veterans Affairs Grant [IK2BX002683]
- National Institute of General Medical Sciences from the National Institutes of Health [P41 GM103403]
- NIH-ORIP HEI [S10OD021527]
- DOE Office of Science by Argonne National Laboratory [DE-AC02-06CH11357]
G protein-coupled receptors (GPCRs) activate heterotrimeric G proteins by mediating a GDP to GTP exchange in the Ga subunit. This leads to dissociation of the heterotrimer into GaGTP and G beta gamma dimer. The Ga-GTP and G beta gamma dimer each regulate a variety of downstream pathways to control various aspects of human physiology. Dysregulated G beta gamma-signaling is a central element of various neurological and cancer-related anomalies. However, G beta gamma also serves as a negative regulator of Ga 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 G beta gamma dimer. Nb5 responds to all combinations of beta-subtypes and.-subtypes and competes with other G beta gamma-regulatory proteins for a common binding site on the G beta gamma dimer. Despite its inhibitory effect on G beta gamma-mediated signaling, Nb5 has no effect on G alpha(q)-mediated and G alpha(s)-mediated signaling events in living cells.
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