Figure 3. BBS1, BBS2, BBS7 and BBS9 are homologous proteins with similarities to the clathrin adaptor proteins.

(a) Location of BBS1, BBS2, BBS7, and BBS9 in the BBSome, colored except for their β-propeller domains. GAE heterodimers shown in panels c and d are boxed. In the rotated view all non-colored subunits are removed for clarity. (b) Heterodimerization of BBS2 and BBS7 involves the hx-GAE module. (c) Heterodimerization of BBS1 and BBS9. (d) Superposition of BBS9^GAE with the GAE domain of AP-1 clathrin adaptor subunit γ-like 2 reveals that the heterodimerization interface with BBS1^GAE would occlude the substrate binding pocket. (e) The GAE-pf module of BBS2, BBS7 and BBS9 resembles the equivalent module of the AP-2 clathrin adaptor α2-adaptin. While BBS9^GAE-pf superposes closely with α2-adaptin, the GAE and pf domains of BBS2 and BBS7 (inset) adopt different orientations relative to one another.

Figure 3—figure supplement 1. Topology of the BBSome GAE and platform (pf) domains.

(a) Three-dimensional model of the BBS1^GAE domain with β-strands colored. (b) Topology diagrams for the GAE domains of BBS1, BBS2, BBS7, and BBS9 following the color scheme in panel a. BBS7^GAE and BBS9^GAE have strand insertions (shown in gray) between the β3 and β4 strands that contribute to different β-sheets in the two subunits. (c) The topology of a GAE domain from the clathrin adaptor protein GGA3 (PDB: 1P4U). Compared to the clathrin adaptor GAE domain, the β4 strand (green) of the GAE domains of the BBSome contributes to the other β-sheet. (d) Three-dimensional model of the BBS7^pf domain with secondary structure elements colored. (e) Topology diagram of BBS7^pf following the color scheme in panel d. BBS2^pf and BBS9^pf share the same topology as BBS7^pf. (f) The platform domain of the AP-2 clathrin adaptor α-appendage has an additional N-terminal α-helix and but lacks the C-terminal β-strand found in the BBSome pf domains.