Movie
Controller
Structure viewers
About EMN Papers
+Search query
-Structure paper
| Title | Cryo-EM structures of the human endolysosomal TRPML3 channel in three distinct states. |
|---|---|
| Journal, issue, pages | Nat Struct Mol Biol, Vol. 24, Issue 12, Page 1146-1154, Year 2017 |
| Publish date | Nov 6, 2017 |
 Authors | Xiaoyuan Zhou / Minghui Li / Deyuan Su / Qi Jia / Huan Li / Xueming Li / Jian Yang /   |
| PubMed Abstract | 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. |
 External links | Nat Struct Mol Biol / PubMed:29106414 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 3.62 - 4.65 Å |
| Structure data | EMDB-7018, PDB-6aye: |
| Chemicals |  ChemComp-NAG: |
| Source |
|
 Keywords |  TRANSPORT PROTEIN / ion channel / TRP channel / lysosomal |
