6V1Q

Two-pore channel 3

Summary for 6V1Q

• Entry DOI: 10.2210/pdb6v1q/pdb
• EMDB information: 21015
• Descriptor: Two pore channel 3, SODIUM ION (2 entities in total)
• Functional Keywords: voltag-gated ion channel, two-pore channel, tpc3, membrane protein
• Biological source: Danio rerio (Zebrafish)
• Total number of polymer chains: 2
• Total formula weight: 177571.32

Authors

Dickinson, M.S.,Stroud, R.M. (deposition date: 2019-11-20, release date: 2019-12-04, Last modification date: 2024-03-06)

Primary citation

Dickinson, M.S.,Myasnikov, A.,Eriksen, J.,Poweleit, N.,Stroud, R.M.
Resting state structure of the hyperdepolarization activated two-pore channel 3.
Proc.Natl.Acad.Sci.USA, 117:1988-1993, 2020

PubMed Abstract: Voltage-gated ion channels endow membranes with excitability and the means to propagate action potentials that form the basis of all neuronal signaling. We determined the structure of a voltage-gated sodium channel, two-pore channel 3 (TPC3), which generates ultralong action potentials. TPC3 is distinguished by activation only at extreme membrane depolarization (V ∼ +75 mV), in contrast to other TPCs and Na channels that activate between -20 and 0 mV. We present electrophysiological evidence that TPC3 voltage activation depends only on voltage sensing domain 2 (VSD2) and that each of the three gating arginines in VSD2 reduces the activation threshold. The structure presents a chemical basis for sodium selectivity, and a constricted gate suggests a closed pore consistent with extreme voltage dependence. The structure, confirmed by our electrophysiology, illustrates the configuration of a bona fide resting state voltage sensor, observed without the need for any inhibitory ligand, and independent of any chemical or mutagenic alteration.

PubMed: 31924746
DOI: 10.1073/pnas.1915144117

Experimental method

ELECTRON MICROSCOPY (3.11 Å)