6rmv | pdb_00006rmv
The crystal structure of a TRP channel peptide bound to a G protein beta gamma heterodimer
Structural highlights
FunctionGBG2_MOUSE 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 PubMedTRPM3 channels play important roles in the detection of noxious heat and in inflammatory thermal hyperalgesia. The activity of these ion channels in somatosensory neurons is tightly regulated by micro-opioid receptors through the signaling of Gbetagamma proteins, thereby reducing TRPM3-mediated pain. We show here that Gbetagamma directly binds to a domain of 10 amino acids in TRPM3 and solve a cocrystal structure of this domain together with Gbetagamma. Using these data and mutational analysis of full-length proteins, we pinpoint three amino acids in TRPM3 and their interacting partners in Gbeta1 that are individually necessary for TRPM3 inhibition by Gbetagamma. The 10-amino-acid Gbetagamma-interacting domain in TRPM3 is subject to alternative splicing. Its inclusion in or exclusion from TRPM3 channel proteins therefore provides a mechanism for switching on or off the inhibitory action that Gbetagamma proteins exert on TRPM3 channels. The structural basis for an on-off switch controlling Gbetagamma-mediated inhibition of TRPM3 channels.,Behrendt M, Gruss F, Enzeroth R, Dembla S, Zhao S, Crassous PA, Mohr F, Nys M, Louros N, Gallardo R, Zorzini V, Wagner D, Economou A, Rousseau F, Schymkowitz J, Philipp SE, Rohacs T, Ulens C, Oberwinkler J Proc Natl Acad Sci U S A. 2020 Oct 29. pii: 2001177117. doi:, 10.1073/pnas.2001177117. PMID:33122432[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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