1.A.14.2.3
The 7 TMS proton-sensitive Ca²⁺ leak channel, YetJ.  The activity and high resolution 3-d structure have been determined (Chang et al. 2014). BsYetJ in lipid nanodiscs is structurally different from those crystallized in detergents. Li et al. 2020 showed that the BsYetJ conformation is pH-sensitive in the apo state (lacking calcium), whereas in a calcium-containing solution, it is stuck in an intermediate state, inert to pH changes. Only when the transmembrane calcium gradient is established can the calcium-release activity of holo-BsYetJ occur and be mediated by pH-dependent conformational changes, suggesting a dual gating mechanism. Conformational substates involved in the process and a key residue, D171, relevant to the gating of calcium were identified. Thus, BsYetJ/TMBIM6 is a pH-dependent, voltage-gated calcium channel (Li et al. 2020). The transmembrane BAX inhibitor-1-containing motif 6 (TMBIM6) protein may modulate apoptosis by regulating calcium homeostasis in the endoplasmic reticulum (ER). Lan et al. 2023 investigated all negatively charged residues in BsYetJ, a bacterial homolog of TMBIM6. They reconstituted BsYetJ in membrane vesicles with a lipid composition similar to that of the ER. The charged residues E49 and R205 work together as a major gate, regulating calcium conductance in these ER-like lipid vesicles. However, these residues become largely inactive when reconstituted in other lipid environments. D195 acts as a minor filter compared to the E49-R205 dyad (Lan et al. 2023).