7DYS
CryoEM structure of full length mouse TRPML2
Summary for 7DYS
| Entry DOI | 10.2210/pdb7dys/pdb |
| EMDB information | 30924 |
| Descriptor | Mucolipin-2 (1 entity in total) |
| Functional Keywords | transient receptor potential mucolipin channels, trp channel, trpml2, membrane protein |
| Biological source | Mus musculus (house mouse) |
| Total number of polymer chains | 4 |
| Total formula weight | 240041.03 |
| Authors | Song, X.J.,Li, J.,Duan, J.J.,Zhang, J. (deposition date: 2021-01-22, release date: 2022-03-23, Last modification date: 2024-11-13) |
| Primary citation | Song, X.,Li, J.,Tian, M.,Zhu, H.,Hu, X.,Zhang, Y.,Cao, Y.,Ye, H.,McCormick, P.J.,Zeng, B.,Fu, Y.,Duan, J.,Zhang, J. Cryo-EM structure of mouse TRPML2 in lipid nanodiscs. J.Biol.Chem., 298:101487-101487, 2022 Cited by PubMed Abstract: In mammalians, transient receptor potential mucolipin ion channels (TRPMLs) exhibit variable permeability to cations such as Ca, Fe, Zn, and Na and can be activated by the phosphoinositide PI(3,5)P2 in the endolysosomal system. Loss or dysfunction of TRPMLs has been implicated in lysosomal storage disorders, infectious diseases, and metabolic diseases. TRPML2 has recently been identified as a mechanosensitive and hypotonicity-sensitive channel in endolysosomal organelles, which distinguishes it from TRPML1 and TRPML3. However, the molecular and gating mechanism of TRPML2 remains elusive. Here, we present the cryo-EM structure of the full-length mouse TRPML2 in lipid nanodiscs at 3.14 Å resolution. The TRPML2 homotetramer structure at pH 7.4 in the apo state reveals an inactive conformation and some unique features of the extracytosolic/luminal domain and voltage sensor-like domain that have implications for the ion-conducting pathway. This structure enables new comparisons between the different subgroups of TRPML channels with available structures and provides structural insights into the conservation and diversity of TRPML channels. These comparisons have broad implications for understanding a variety of molecular mechanisms of TRPMLs in different pH conditions, including with and without bound agonists and antagonists. PubMed: 34915027DOI: 10.1016/j.jbc.2021.101487 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.18 Å) |
Structure validation
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