Structural conservation of residues in BH1 and BH2 domains of Bcl-2 family proteins

Abstract 

The sequence of Bcl-2 homology domains, BH1 and BH2, is known to be conserved among anti- and pro-apoptotic members of Bcl-2 family proteins. But structural conservation of these domains with respect to functionally active residues playing role in heterodimerization-mediated regulation of apoptosis has never been elucidated. Here, we have suggested the formation of an active site by structurally conserved residues in BH1 (glycine, arginine) and BH2 (tryptophan) domains of Bcl-2 family members, which also accounts for the functional effect of known mutations in BH1 (G145A, G145E) and BH2 (W188A) domains of Bcl-2.

Abbreviations: BH, Bcl-2 Homology, G, Glycine, A, Alanine, K, Lysine, E, Glutamic acid, R, Arginine, W, Tryptophan, 1MAZ, E. coli Bcl-X_L (GI 2098338), 1BXL, E. coli Bcl-X_L/Bak complex (GI 2624621), 1PQ0, Mouse Bcl-X_L (GI 37927566), 1PQ1, Mouse Bcl-X_L/Bim complex (GI 37927568), 1WSX, Mouse Mcl-1 (GI 56966992), 1AF3, Rat Bcl-X_L (GI 2392082), 1G5M, Human Bcl-2 Isoform 1 (GI 13786963), 1GJH, Human Bcl-2 Isoform 2 (GI 14719780), 1LXL, Human Bcl-X_L (GI 2098333), 1R2D, Human Bcl-X_L (GI 42543462), 1G5J, Human Bcl-X_L/Bad complex (GI 13096159), 1MK3, Human Bcl-W (GI 31615587), 1F16, Human Bax-alpha (GI 11513492), 1Q59A, EB2 virus BHRF-1 protein (GI 37927821), 1K3K, Kaposi’s sarcoma virus 2 (GI 20663999), 1TY4, C. elegans CED-9/EGL-1 complex (GI 55670071)

Keywords: Structural conservation, Active site prediction, Heterodimerization, Docking, Mutation