EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Structure-function analyses of the ion channel TRPC3 reveal that its cytoplasmic domain allosterically modulates channel gating.
ジャーナル・号・ページ	J Biol Chem, Vol. 293, Issue 41, Page 16102-16114, Year 2018
掲載日	2018年10月12日
著者	Francisco Sierra-Valdez / Caleigh M Azumaya / Luis O Romero / Terunaga Nakagawa / Julio F Cordero-Morales /
PubMed 要旨	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 ...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.
リンク	J Biol Chem / PubMed:30139744 / PubMed Central
手法	EM (単粒子)
解像度	4.0 - 5.8 Å
構造データ	7823 6d7l EMDB-7823, PDB-6d7l: Cytoplasmic domain of TRPC3 手法: EM (単粒子) / 解像度: 4.0 Å 7940 6djr 6djs EMDB-7940, PDB-6djr: Full-length human TRPC3 in GDN PDB-6djs: Hybrid model of TRPC3 in GDN 手法: EM (単粒子) / 解像度: 5.8 Å
由来	homo sapiens (ヒト)
キーワード	TRANSPORT PROTEIN (運搬体タンパク質) / TRP channel (TRPチャネル) / Ion Channel (イオンチャネル) / Membrane protein (膜タンパク質) / cerebellum (小脳) / moonwalker (ムーンウォーカー (映画))