Structural and Biochemical Bases for the Inhibition of Autophagy and Apoptosis by Viral BCL-2 of Murine γ-Herpesvirus 68
Figure 2
Beclin1 Has a BH3-Like Domain Containing an Atypical Threonine and an Exposed Hydrophobic Patch
(A) A structural comparison of the M11–Beclin1(101–150) (left) and the BCL-XL–BAD complexes (right). M11 and BCL-XL are shown as surface models. The Beclin1 and BAD residues shown in sticks correspond to the five BH3 residues that are critical for the interactions with antiapoptotic BCL-2 family members [21]. They occupy equivalent positions at the BH3-binding groove in the two structures. The surface coloring scheme is as follows: yellow for Val, Leu, Ile, Tyr, Phe, Trp, Met, and Ala; blue for Lys, Arg, and His; red for Glu and Asp; gray for other amino acids.
(B) Sequence comparison of the BH3-like domain of mouse Beclin1 with various BH3 domains. Conserved residues are highlighted by red or pink columns. The arrows indicate the five BH3 residues shown in (A). Of these, Thr117 of Beclin1 (red arrow) is not conserved.
(C) Sequence alignment. The BH3-like domains of Beclin1 orthologues are aligned (mm, mouse; hs, human; xl, Xenopus laevis; tr, Takifugu rubripes; dm, Drosophila melanogaster; sc, Saccharomyces cerevisiae). The arrows at the top indicate the BH3 residues shown in (A). These residues are highly conserved throughout species, except for Thr117 of mouse Beclin1, which is conserved only in the vertebrates. The conserved hydrophobic residues of Beclin1 exposed in the structure are indicated by the blue arrows at the bottom.
(D) α-helical wheel representation. The Beclin1 α-helix bound to M11 is compared with the BAD α-helix bound to BCL-XL. The Beclin1 helix has a hydrophobic patch (indicated by an asterisk) on the opposite side of the BH3-binding groove, unlike the BAD helix.