Protein Family Models

Programmed cell-death involves a set of Bcl-2 family proteins, some of which inhibit apoptosis (Bcl-2 and Bcl-XL) and some of which promote it (Bax and Bak). Human Bax inhibitor, BI-1, is an evolutionarily conserved integral membrane protein containing multiple membrane-spanning segments predominantly localised to intracellular membranes. It has 6-7 membrane-spanning domains. The C termini of the mammalian BI-1 proteins are comprised of basic amino acids resembling some nuclear targeting sequences, but otherwise the predicted proteins lack motifs that suggest a function. As plant BI-1 appears to localise predominantly to the ER, we hypothesized that plant BI-1 could also regulate cell death triggered by ER stress [2]. BI-1 appears to exert its effect through an interaction with calmodulin [3]. The budding yeast member of this family has been found unexpectedly to encode a BH3 domain-containing protein (Ybh3p) that regulates the mitochondrial pathway of apoptosis in a phylogenetically conserved manner [4]. Examination of the crystal structure of a bacterial member of this family shows that these proteins mediate a calcium leak across the membrane that is pH-dependent. Calcium homoeostasis balances passive calcium leak with active calcium uptake. The structure exists in a pore-closed and pore-open conformation, at pHs of 8 and 6 respectively, and the pore can be opened by intracrystalline transition; together these findings suggest that pH controls the conformational transition [5]. [1]. 14671021. Dissection of Arabidopsis Bax inhibitor-1 suppressing Bax-, hydrogen peroxide-, and salicylic acid-induced cell death. Kawai-Yam. TRUNCATED at 1650 bytes (from Pfam)

Date:

2024-10-16