6RMV

The crystal structure of a TRP channel peptide bound to a G protein beta gamma heterodimer

Summary for 6RMV

• Entry DOI: 10.2210/pdb6rmv/pdb
• Descriptor: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, Transient receptor potential cation channel, subfamily M, member 3, ... (5 entities in total)
• Functional Keywords: g protein, trp channel, inhibitor, protein binding
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 3
• Total formula weight: 47286.39

Authors

Gruss, F.,Oberwinkler, J.,Ulens, C. (deposition date: 2019-05-07, release date: 2020-10-14, Last modification date: 2024-01-24)

Primary citation

Behrendt, M.,Gruss, F.,Enzeroth, R.,Dembla, S.,Zhao, S.,Crassous, P.A.,Mohr, F.,Nys, M.,Louros, N.,Gallardo, R.,Zorzini, V.,Wagner, D.,Economou, A.,Rousseau, F.,Schymkowitz, J.,Philipp, S.E.,Rohacs, T.,Ulens, C.,Oberwinkler, J.
The structural basis for an on-off switch controlling G beta gamma-mediated inhibition of TRPM3 channels.
Proc.Natl.Acad.Sci.USA, 117:29090-29100, 2020

PubMed Abstract: TRPM3 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 µ-opioid receptors through the signaling of Gβγ proteins, thereby reducing TRPM3-mediated pain. We show here that Gβγ directly binds to a domain of 10 amino acids in TRPM3 and solve a cocrystal structure of this domain together with Gβγ. Using these data and mutational analysis of full-length proteins, we pinpoint three amino acids in TRPM3 and their interacting partners in Gβ that are individually necessary for TRPM3 inhibition by Gβγ. The 10-amino-acid Gβγ-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 Gβγ proteins exert on TRPM3 channels.

PubMed: 33122432
DOI: 10.1073/pnas.2001177117

Experimental method

X-RAY DIFFRACTION (1.94 Å)