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	Symmetry-driven gating of TRPM8 by PIP and menthol.
ジャーナル・号・ページ	Nat Commun, Vol. 17, Issue 1, Year 2026
掲載日	2026年7月21日
著者	Sun-Hong Kim / Chansik Hong / Hyunwoo Park / Youngchang Ju / Youngsoo Hwang / Jinhyeong Kim / Sangho Ji / Wookyung Yu / Insuk So / Hyung Ho Lee /
PubMed 要旨	TRPM8, a cold-activated ion channel, enables mammals to sense cooling agents such as menthol. While PIP is essential for menthol-induced activation of TRPM8, the precise cooperative mechanism and the ...TRPM8, a cold-activated ion channel, enables mammals to sense cooling agents such as menthol. While PIP is essential for menthol-induced activation of TRPM8, the precise cooperative mechanism and the specific binding mode of menthol have remained elusive. Here, we present cryo-EM structures of mouse TRPM8 in diverse conformations, including a PIP-induced two-fold symmetric intermediate and an icilin-bound open state. Our results reveal that PIP binding initiates a symmetry-breaking event, priming the channel for activation through a noncanonical intermediate states. The subsequent binding of cooling agonists promotes a transition back to four-fold symmetry. Notably, we find that menthol stabilizes the PIP-bound state, thereby overcoming channel desensitization, while icilin, in concert with calcium, stabilizes a fully open conformation. Together, these structures illuminate a stepwise activation pathway involving distinct symmetry transitions and define the cooperative allosteric mechanism by which PIP and cooling agonists gate the channel.
リンク	Nat Commun / PubMed:42481499 / PubMed Central
手法	EM (単粒子)
解像度	2.81 - 4.09 Å
構造データ	65116 9vjn EMDB-65116, PDB-9vjn: Cryo-EM structure of TRP melastatin channel in the closed state 手法: EM (単粒子) / 解像度: 3.43 Å 65117 9vjo EMDB-65117, PDB-9vjo: Cryo-EM structure of TRP melastatin channel in the intermediate 1 state 手法: EM (単粒子) / 解像度: 2.82 Å 65118 9vjp EMDB-65118, PDB-9vjp: Cryo-EM structure of TRP melastatin channel in the intermediate 2 state 手法: EM (単粒子) / 解像度: 3.29 Å 65119 9vjq EMDB-65119, PDB-9vjq: Cryo-EM structure of TRP melastatin channel with menthol 手法: EM (単粒子) / 解像度: 2.9 Å 65120 9vjr EMDB-65120, PDB-9vjr: Cryo-EM structure of TRP melastatin channel with icilin 手法: EM (単粒子) / 解像度: 3.1 Å 65204 9vn9 EMDB-65204, PDB-9vn9: Cryo-EM structure of TRP melastatin channel in the intermediate 3 state 手法: EM (単粒子) / 解像度: 3.48 Å 65205 9vna EMDB-65205, PDB-9vna: Cryo-EM structure of TRP melastatin channel in the desensitized state, with CHS 手法: EM (単粒子) / 解像度: 3.25 Å 65206 9vnb EMDB-65206, PDB-9vnb: Cryo-EM structure of TRP melastatin channel in the desensitized state, without CHS 手法: EM (単粒子) / 解像度: 2.81 Å 65207 9vnc EMDB-65207, PDB-9vnc: Cryo-EM structure of TRP melastatin channel in the desensitized state, with icilin 手法: EM (単粒子) / 解像度: 3.45 Å EMDB-69908: Cryo-EM structure of TRP melastatin channel in the desensitized state, with icilin (10min) 手法: EM (単粒子) / 解像度: 3.46 Å EMDB-69909: Cryo-EM structure of TRP melastatin channel with icilin (10min) 手法: EM (単粒子) / 解像度: 3.08 Å EMDB-69929: Cryo-EM structure of TRP melastatin channel in the putative intermediate 3, without CHS 手法: EM (単粒子) / 解像度: 3.71 Å EMDB-69930: Cryo-EM structure of TRP melastatin channel in the putative desensitized state, without CHS 手法: EM (単粒子) / 解像度: 3.1 Å EMDB-69932: Cryo-EM structure of TRP melastatin channel in the putative intermediate 2 state, with EGTA 手法: EM (単粒子) / 解像度: 3.58 Å EMDB-69933: Cryo-EM structure of TRP melastatin channel in the putative twofold intermediate 1 state, with EGTA 手法: EM (単粒子) / 解像度: 4.09 Å EMDB-69934: Cryo-EM structure of TRP melastatin channel in the putative desensitized state, with EGTA 手法: EM (単粒子) / 解像度: 3.95 Å
化合物	ChemComp-Y01: CHOLESTEROL HEMISUCCINATE ChemComp-POV: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate / リン脂質YM ChemComp-PIO: [(2R)-2-octanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phosphoryl]oxy-propyl] octanoate ChemComp-CA: Unknown entry 化合物画像なし ChemComp-XUQ: Unknown entry ChemComp-KX7: Icilin ChemComp-CLR*: CHOLESTEROL
由来	mus musculus (ハツカネズミ)
キーワード	MEMBRANE PROTEIN / TRP