(A) Schematics of the predicted domain organization of each BBSome subunit. BBS4 and BBS8 respectively have 13 and 12.5 tetratricopeptide repeats (TPR). BBS1, BBS2, BBS7 and BBS9 each consist of a β-propeller followed by an amphipathic helical linker and a γ-adaptin ear domain (GAE). In BBS2, BBS7 and BBS9, the GAE is followed by an α/ β platform domain and α-helix domain. In BBS1, a four-helix bundle is inserted between the second and third blades. BBS5 contains two pleckstrin homology (PH) domains and a 3-helix bundle while BBIP10 is predicted to fold into two coiled-coils.
(B) Structure-based alignment of the proposed GAE modules of BBS1, BBS2, BBS7 and BBS9. The structures used to generate the model of the GAE domain of BBS1 were those of GGA1, AP2©1, AP2®2, AP2α and γCOP. Only the N- and C-terminal six β-strands of the Ig-like folds (respectively labeled A–C and E–G) are shown, in a color gradient that matches the chain topology of the human BBS1 GAE domain model. While the primary sequence identity between solved or predicted structures remains quite low, hydrophobic positions (highlighted) are well conserved. See for details on fold recognitions and secondary structure predictions.
(C) The platform-like modules of BBS2, BBS7 and BBS9 are topological variants of the appendage domains. The C-terminal platform domains of γCOP, βCOP, AP2β2 and AP2α were structurally aligned to the proposed platform-like modules of BBS2, BBS7 and BBS9 as above. β-strands are shown as arrows (labeled I–M) and helices as cylinders (labeled 1–3), color matched to the AP2α structure and the modeled fold of the human BBS7 platform-like module. Intriguingly, β-strand H and helix 1 are missing from BBS2/ 7/ 9, but in turn these gain an additional, conserved C-terminal β-strand (labeled N) that is predicted to form an edge strand (grey) in the platform β-sheet.
(D) Recurring membrane recruitment machinery and structural elements of the canonical coats and of the BBSome. The PIPs that participate in coat complexes binding to membranes in vitro are listed in orange. The Arf-like GTPases that recruit the coat complexes to membranes are listed in black. The β-propeller, α-solenoid and appendage domains are listed in blue, red and green respectively (; Owen et al., 2004).