Solution structure of human saposin C in a detergent environment.
Saposin C is a lysosomal, membrane-binding protein that acts as an activator for the hydrolysis of glucosylceramide by the enzyme glucocerebrosidase. We used high-resolution NMR to determine the three-dimensional solution structure of saposin C in the presence of the detergent sodium dodecyl sulfate (SDS). This structure provides the first representation of membrane bound saposin C at the atomic level. In the presence of SDS, the protein adopts an open conformation with an exposed hydrophobic pocket. In contrast, the previously reported NMR structure of saposin C in the absence of SDS is compact and contains a hydrophobic core that is not exposed to the solvent. NMR data indicate that the SDS molecules interact with the hydrophobic pocket. The structure of saposin C in the presence of SDS is very similar to a monomer in the saposin B homodimer structure. Their comparison reveals possible similarity in the type of protein/lipid interaction as well as structural components differentiating their quaternary structures and functional specificity.
Hawkins
Cheryl A
CA
Laboratory of Biophysical Chemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, 50 Center Drive, Bethesda, MD 20892, USA.
de Alba
Eva
E
Tjandra
Nico
N
D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D011487:Protein Conformation; D049231:Saposins / Q000737:chemistry* / Q000378:metabolism; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry* / Q000378:metabolism; D012996:Solutions
D049231:Saposins; D012996:Solutions; D012967:Sodium Dodecyl Sulfate