6D7L

Cytoplasmic domain of TRPC3

6D7L の概要

• エントリーDOI: 10.2210/pdb6d7l/pdb
• EMDBエントリー: 7823
• 分子名称: Short transient receptor potential channel 3 (1 entity in total)
• 機能のキーワード: trp channel, ion channel, membrane protein, cerebellum, moonwalker, transport protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 391477.12

構造登録者

Sierra-Valdez, F.J.,Azumaya, C.M.,Nakagawa, T.,Cordero-Morales, J.F. (登録日: 2018-04-25, 公開日: 2018-08-29, 最終更新日: 2024-03-13)

主引用文献

Sierra-Valdez, F.,Azumaya, C.M.,Romero, L.O.,Nakagawa, T.,Cordero-Morales, J.F.
Structure-function analyses of the ion channel TRPC3 reveal that its cytoplasmic domain allosterically modulates channel gating.
J. Biol. Chem., 293:16102-16114, 2018

PubMed Abstract: The transient receptor potential ion channels support Ca permeation in many organs, including the heart, brain, and kidney. Genetic mutations in transient receptor potential cation channel subfamily C member 3 (TRPC3) are associated with neurodegenerative diseases, memory loss, and hypertension. To better understand the conformational changes that regulate TRPC3 function, we solved the cryo-EM structures for the full-length human TRPC3 and its cytoplasmic domain (CPD) in the apo state at 5.8- and 4.0-Å resolution, respectively. These structures revealed that the TRPC3 transmembrane domain resembles those of other TRP channels and that the CPD is a stable module involved in channel assembly and gating. We observed the presence of a C-terminal domain swap at the center of the CPD where horizontal helices (HHs) transition into a coiled-coil bundle. Comparison of TRPC3 structures revealed that the HHs can reside in two distinct positions. Electrophysiological analyses disclosed that shortening the length of the C-terminal loop connecting the HH with the TRP helices increases TRPC3 activity and that elongating the length of the loop has the opposite effect. Our findings indicate that the C-terminal loop affects channel gating by altering the allosteric coupling between the cytoplasmic and transmembrane domains. We propose that molecules that target the HH may represent a promising strategy for controlling TRPC3-associated neurological disorders and hypertension.

PubMed: 30139744
DOI: 10.1074/jbc.RA118.005066

実験手法

ELECTRON MICROSCOPY (4 Å)