Structure of the Popeye domain containing proteins. (a) Schematic structure of the human POPDC isoforms. The three POPDC proteins share a similar protein structure. In each case a 20–40 amino acid long extracellular domain (ECD), which harbors one or two N-glycosylation sites (asterisks) is followed by three transmembrane (TM) domains (I–III, black boxes). The cytoplasmic portion of the POPDC proteins consists of the Popeye domain (red box) and the carboxyterminal domain (CTD, yellow box). The phosphate-binding cassette (PBC), which is thought to bind cAMP, consists of the two tetrapeptides DSPE and FQVT. In case of POPDC1, the locations for the KCNK2 (TREK-1) [28] and CAV3 [33] binding sites and the putative dimerization motif [34] are indicated (blue bars). POPDC2 generates three alternative splice products, which differ in their carboxy-terminus labeled by a grey box. Mutations in POPDC1 and POPDC2, which have been identified in patients with muscle and heart disease are indicated above each protein model. (b) 3-D structure of POPDC3. A homology-based structural model was generated with the help of the Phyre 2 algorithm [35]. The resulting structure was visualized with the help of First Glance in JMOL [36].
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