4pgu

Publication Abstract from PubMed

Calcium homeostasis balances passive calcium leak and active calcium uptake. Human Bax inhibitor-1 (hBI-1) is an antiapoptotic protein that mediates a calcium leak and is representative of a highly conserved and widely distributed family, the transmembrane Bax inhibitor motif (TMBIM) proteins. Here, we present crystal structures of a bacterial homolog and characterize its calcium leak activity. The structure has a seven-transmembrane-helix fold that features two triple-helix sandwiches wrapped around a central C-terminal helix. Structures obtained in closed and open conformations are reversibly interconvertible by change of pH. A hydrogen-bonded, pKa (where Ka is the acid dissociation constant)-perturbed pair of conserved aspartate residues explains the pH dependence of this transition, and biochemical studies show that pH regulates calcium influx in proteoliposomes. Homology models for hBI-1 provide insights into TMBIM-mediated calcium leak and cytoprotective activity.

Structural basis for a pH-sensitive calcium leak across membranes.,Chang Y, Bruni R, Kloss B, Assur Z, Kloppmann E, Rost B, Hendrickson WA, Liu Q Science. 2014 Jun 6;344(6188):1131-5. doi: 10.1126/science.1252043. PMID:24904158^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.