Fig. 1

SorCS2 forms a cross-braced homodimer. a Schematic representation of SorCS2 with the different domains colored and the ten blades of the β-propeller numbered. The second PKD domain and the SoMP domain were previously unreported and together with PKD1 constitute the leucine rich repeat region. Predicted N-glycosylation sites (stars), proteolytic processing sites (scissors), pro domain (PRO), transmembrane domain (TM) and intracellular domain (ICD) are also indicated. b Cartoon representation of the structure of the unliganded sSorCS2 dimer (one monomer colored according to (a), the other monomer colored gray). The predicted orientation and connection to the cell surface of sSorCS2 are indicated. Seven residues are lacking between the structure and the two transmembrane helixes. The top faces of the β-propellers are slanted towards the cell membrane. The SoMP domain is folded and interacts with the β-propeller of an opposing monomer, essentially cross-bracing the dimer. c One chain of the sSorCS2 dimer in cartoon representation and colored as in (a). The processing site at S1031⁴ (scissors) resides in a disordered loop that is located close to the cell surface. d SoMP has a fold similar to an RNA Recognition Motif. Superposition of the SorCS2 SoMP domain (red) and the RNA recognition motif of yeast eIF3b⁶⁶ (pdb 3NS5, yellow) (left panel). Topology diagram of SorCS2 SoMP with secondary structure elements indicated (right, panel). Processing site (scissors) as in (c). e Residues involved in dimer formation colored orange for the PKD–PKD interface and blue for the SoMP–VPS10p interface