+検索条件
-Structure paper
タイトル | Cryo-EM structures of the human endolysosomal TRPML3 channel in three distinct states. |
---|---|
ジャーナル・号・ページ | Nat Struct Mol Biol, Vol. 24, Issue 12, Page 1146-1154, Year 2017 |
掲載日 | 2017年11月6日 |
著者 | Xiaoyuan Zhou / Minghui Li / Deyuan Su / Qi Jia / Huan Li / Xueming Li / Jian Yang / |
PubMed 要旨 | TRPML3 channels are mainly localized to endolysosomes and play a critical role in the endocytic pathway. Their dysfunction causes deafness and pigmentation defects in mice. TRPML3 activity is ...TRPML3 channels are mainly localized to endolysosomes and play a critical role in the endocytic pathway. Their dysfunction causes deafness and pigmentation defects in mice. TRPML3 activity is inhibited by low endolysosomal pH. Here we present cryo-electron microscopy (cryo-EM) structures of human TRPML3 in the closed, agonist-activated, and low-pH-inhibited states, with resolutions of 4.06, 3.62, and 4.65 Å, respectively. The agonist ML-SA1 lodges between S5 and S6 and opens an S6 gate. A polycystin-mucolipin domain (PMD) forms a luminal cap. S1 extends into this cap, forming a 'gating rod' that connects directly to a luminal pore loop, which undergoes dramatic conformational changes in response to low pH. S2 extends intracellularly and interacts with several intracellular regions to form a 'gating knob'. These unique structural features, combined with the results of electrophysiological studies, indicate a new mechanism by which luminal pH and other physiological modulators such as PIP regulate TRPML3 by changing S1 and S2 conformations. |
リンク | Nat Struct Mol Biol / PubMed:29106414 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.62 - 4.65 Å |
構造データ | |
化合物 | ChemComp-NAG: |
由来 |
|
キーワード | TRANSPORT PROTEIN / ion channel / TRP channel / lysosomal |