The putative phospholipid-binding site, which is the active site of Tafazzin, is a 57 amino acid cleft with two open ends and positively charged residues. In addition, tafazzin localizes to the membrane leaflets facing the intermembrane space (IMS), which is crucial for remodeling. Tafazzin differs from phospholipases in that it contains a conserved histidine residue, His-77, as part of the conserved HX4D motif seen in acyltransferases. This motif is responsible for facilitating the Asp-His dyad mechanism seen in many serine proteases. Many unique forms of tafazzin have been identified, with lengths from 129 to 292 amino acids. Tafazzin has at least 4 different isoforms. It has a molecular weight around 35kDa but may also appear in lower molecular weights due to species differences in isoform expression. 7 functional classes of TAFAZZIN mutations have been classified based on the pathogenic loss-of-function mechanisms of each mutation.
