+検索条件
-Structure paper
タイトル | Structural basis of cooling agent and lipid sensing by the cold-activated TRPM8 channel. |
---|---|
ジャーナル・号・ページ | Science, Vol. 363, Issue 6430, Year 2019 |
掲載日 | 2019年3月1日 |
![]() | Ying Yin / Son C Le / Allen L Hsu / Mario J Borgnia / Huanghe Yang / Seok-Yong Lee / ![]() |
PubMed 要旨 | Transient receptor potential melastatin member 8 (TRPM8) is a calcium ion (Ca)-permeable cation channel that serves as the primary cold and menthol sensor in humans. Activation of TRPM8 by cooling ...Transient receptor potential melastatin member 8 (TRPM8) is a calcium ion (Ca)-permeable cation channel that serves as the primary cold and menthol sensor in humans. Activation of TRPM8 by cooling compounds relies on allosteric actions of agonist and membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP), but lack of structural information has thus far precluded a mechanistic understanding of ligand and lipid sensing by TRPM8. Using cryo-electron microscopy, we determined the structures of TRPM8 in complex with the synthetic cooling compound icilin, PIP, and Ca, as well as in complex with the menthol analog WS-12 and PIP Our structures reveal the binding sites for cooling agonists and PIP in TRPM8. Notably, PIP binds to TRPM8 in two different modes, which illustrate the mechanism of allosteric coupling between PIP and agonists. This study provides a platform for understanding the molecular mechanism of TRPM8 activation by cooling agents. |
![]() | ![]() ![]() ![]() |
手法 | EM (単粒子) |
解像度 | 3.4 - 4.3 Å |
構造データ | EMDB-0487, PDB-6nr2: |
化合物 | ![]() ChemComp-KXP: ![]() ChemComp-KXS: ![]() ChemComp-KX7: ![]() ChemComp-CA: |
由来 |
|
![]() | TRANSPORT PROTEIN / ion channel / TRP channel / TRPM channel / TRPM8 channel / cold sensing / lipid sensing / menthol / icilin / WS-12 / PI(4 / 5)P2 / cooling agent / MEMBRANE PROTEIN / calcium-permeable ion channel / calcium-permeable channel |