The Sema domain occurs in semaphorins, which are a large family of secreted and transmembrane proteins, some of which function as repellent signals during axon guidance. Sema domains also occur in plexins [ PUBMED:9875845 ], receptors for multiple classes of semaphorins, in hepatocyte growth factor receptor, and in viral … expand

The Sema domain occurs in semaphorins, which are a large family of secreted and transmembrane proteins, some of which function as repellent signals during axon guidance. Sema domains also occur in plexins [ PUBMED:9875845 ], receptors for multiple classes of semaphorins, in hepatocyte growth factor receptor, and in viral proteins [ PUBMED:9712866 ].

The Sema domain is characterised by a conserved set of cysteine residues, which form four disulphide bonds to stabilise the structure. The Sema domain fold is a variation of the β propeller topology, with seven blades radially arranged around a central axis. Each blade contains a four-stranded (strands A to D) antiparallel β sheet. The inner strand of each blade (A) lines the channel at the centre of the propeller, with strands B and C of the same repeat radiating outward, and strand D of the next repeat forming the outer edge of the blade. The large size of the Sema domain is not due to a single inserted domain but results from the presence of additional secondary structure elements inserted in most of the blades. The Sema domain uses a 'loop and hook' system to close the circle between the first and the last blades. The blades are constructed sequentially with an N-terminal β-strand closing the circle by providing the outermost strand (D) of the seventh (C-terminal) blade. The β-propeller is further stabilised by an extension of the N terminus, providing an additional, fifth β-strand on the outer edge of blade 6 [ PUBMED:12925274 PUBMED:12958590 PUBMED:15167892 ].