The Sema domain is characterised by a conserved set of cysteine residues, which form four disulfide bonds to stabilise the structure.

The Sema domain fold is a variation of the beta propeller topology, with seven blades radially arranged around a central axis.

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 beta-propeller is further stabilized by an extension of the N-terminus, providing an additional, fifth beta-strand on the outer edge of blade 6.