Prosaposin is a precursor of four cofactors, saposins A, B,C and D, which are required for hydrolysis of sphingolipids by lysosomal enzymes (1). Prosaposin contains multiple glycans and was found to be an obligate substrate for the UDP-glucose:glycoprotein glucosyl transferase 1 (UGT1), a folding sensor that resides in the ER and supports folding of secretory proteins(1). Deficiency of UGT1 causes defects in prosaposin maturation(1). Prosaposin is cleaved in the lysosome into the four saposins. The four saposins are members of the larger family of saposin –like proteins(2). The saposin motif is characterized by six that form three intramolecular disulfide bonds(2). In this representation is shown the saposin C domain of prosaposin. Saposin C adopts a monomeric saposin fold with four α-helices, where the third helix shows a highly localized kink (2). Shown in green is the of an Asn residue that gets modified in the ER in the prosaposin precursor by addition of a glycan before it gets cleaved in the lysosome.
1- Bradley R. Pearse,Taku Tamura,Johan C. Sunryd,Gregory A. Grabowski, Randal J. Kaufman and Daniel N. Hebert. The role of UDP-Glc:glycoprotein glucosyltransferase 1 in the maturation of an obligate substrate prosaposin. Journal of Cell Biology. 189; 829-841 (2010)
2- Victoria E. Ahn, Paul Leyko, Jean-René Alattia, Lu Chen, and Gilbert G. Privé. Crystal structures of saposin A and C. Protein Science 15;1849-1857 (2006)