Ion and pH Sensitivity of a TMBIM Ca²⁺ Channel.

ABSTRACT: The anti-apoptotic transmembrane Bax inhibitor motif (TMBIM) containing protein family regulates Ca²⁺ homeostasis, cell death, and the progression of diseases including cancers. The recent crystal structures of the TMBIM homolog BsYetJ reveal a conserved Asp171-Asp195 dyad that is proposed in regulating a pH-dependent Ca²⁺ translocation. Here we show that BsYetJ mediates Ca²⁺ fluxes in permeabilized mammalian cells, and its interaction with Ca²⁺ is sensitive to protons and other cations. We report crystal structures of BsYetJ in additional states, revealing the flexibility of the dyad in a closed state and a pore-opening mechanism. Functional studies show that the dyad is responsible for both Ca²⁺ affinity and pH dependence. Computatio

SUBMITTER: Guo G 

PROVIDER: S-EPMC6560632 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature