Crystal structures of saposins A and C.
Saposins A and C are sphingolipid activator proteins required for the lysosomal breakdown of galactosylceramide and glucosylceramide, respectively. The saposins interact with lipids, leading to an enhanced accessibility of the lipid headgroups to their cognate hydrolases. We have determined the crystal structures of human saposins A and C to 2.0 Angstroms and 2.4 Angstroms, respectively, and both reveal the compact, monomeric saposin fold. We confirmed that these two proteins were monomeric in solution at pH 7.0 by analytical centrifugation. However, at pH 4.8, in the presence of the detergent C(8)E(5), saposin A assembled into dimers, while saposin C formed trimers. Saposin B was dimeric under all conditions tested. The self-association of the saposins is likely to be relevant to how these small proteins interact with lipids, membranes, and hydrolase enzymes.
Ahn
Victoria E
VE
Department of Medical Biophysics, University of Toronto, Canada.
Leyko
Paul
P
Alattia
Jean-René
JR
Chen
Lu
L
Privé
Gilbert G
GG
D000595:Amino Acid Sequence; D003460:Crystallization; D018360:Crystallography, X-Ray; D003902:Detergents; D019281:Dimerization; D004987:Ethers; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011092:Polyethylene Glycols; D020836:Protein Structure, Quaternary; D049231:Saposins / Q000737:chemistry*; D016415:Sequence Alignment; D014461:Ultracentrifugation
D003902:Detergents; D004987:Ethers; D049231:Saposins; C489458:pentaethylene glycol n-octyl ether; D011092:Polyethylene Glycols