6NQ0
Cryo-EM structure of human TPC2 channel in the ligand-bound open state
Summary for 6NQ0
| Entry DOI | 10.2210/pdb6nq0/pdb |
| EMDB information | 0477 0478 0479 |
| Descriptor | Two pore calcium channel protein 2, (2R)-3-{[(S)-hydroxy{[(1S,2R,3R,4S,5S,6R)-2,4,6-trihydroxy-3,5-bis(phosphonooxy)cyclohexyl]oxy}phosphoryl]oxy}propane-1,2-diyl dioctanoate (2 entities in total) |
| Functional Keywords | channel, lysosome, transport protein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 172836.79 |
| Authors | |
| Primary citation | She, J.,Zeng, W.,Guo, J.,Chen, Q.,Bai, X.,Jiang, Y. Structural mechanisms of phospholipid activation of the human TPC2 channel. Elife, 8:-, 2019 Cited by PubMed Abstract: Mammalian two-pore channels (TPCs) regulate the physiological functions of the endolysosome. Here we present cryo-EM structures of human TPC2 (HsTPC2), a phosphatidylinositol 3,5-bisphosphate (PI(3,5)P)-activated, Na selective channel, in the ligand-bound and apo states. The apo structure captures the closed conformation, while the ligand-bound form features the channel in both open and closed conformations. Combined with functional analysis, these structures provide insights into the mechanism of PI(3,5)P-regulated gating of TPC2, which is distinct from that of TPC1. Specifically, the endolysosome-specific PI(3,5)P binds at the first 6-TM and activates the channel - independently of the membrane potential - by inducing a structural change at the pore-lining inner helix (IS6), which forms a continuous helix in the open state but breaks into two segments at Gly317 in the closed state. Additionally, structural comparison to the voltage-dependent TPC1 structure allowed us to identify Ile551 as being responsible for the loss of voltage dependence in TPC2. PubMed: 30860481DOI: 10.7554/eLife.45222 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.7 Å) |
Structure validation
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