6NQ7

Crystal structure of YetJ from Bacillus Subtilis crystallized in lipidic cubic phase

Summary for 6NQ7

• Entry DOI: 10.2210/pdb6nq7/pdb
• Descriptor: Uncharacterized protein YetJ, GADOLINIUM ATOM (3 entities in total)
• Functional Keywords: ca2+ channel structure, closed state, ph sensor, membrane protein
• Biological source: Bacillus subtilis (strain 168)
• Total number of polymer chains: 1
• Total formula weight: 23471.16

Authors

Guo, G.,Chang, Y.,Liu, Q. (deposition date: 2019-01-19, release date: 2019-04-17, Last modification date: 2023-10-11)

Primary citation

Guo, G.,Xu, M.,Chang, Y.,Luyten, T.,Seitaj, B.,Liu, W.,Zhu, P.,Bultynck, G.,Shi, L.,Quick, M.,Liu, Q.
Ion and pH Sensitivity of a TMBIM Ca2+Channel.
Structure, 27:1013-1021.e3, 2019

PubMed Abstract: The anti-apoptotic transmembrane Bax inhibitor motif (TMBIM) containing protein family regulates Ca 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 Ca translocation. Here we show that BsYetJ mediates Ca fluxes in permeabilized mammalian cells, and its interaction with Ca 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 Ca affinity and pH dependence. Computational simulations suggest that protonation of Asp171 weakens its interaction with Arg60, leading to an open state. Our integrated analysis provides insights into the regulation of the BsYetJ Ca channel that may inform understanding of human TMBIM proteins regarding their roles in cell death and diseases.

PubMed: 30930064
DOI: 10.1016/j.str.2019.03.003

Experimental method

X-RAY DIFFRACTION (2.5 Å)