期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 109, 期 8, 页码 2908-2912出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1115743109
关键词
protein-lipid complex; X-ray crystallography; molecular dynamics; Krabbe disease
资金
- Canada Foundation for Innovation under the auspices of Compute Canada
- Government of Ontario
- Ontario Research Fund-Research Excellence
- University of Toronto
- Canadian Institutes of Health Research (CIHR)
- Natural Sciences and Engineering Research Council of Canada
- Canada Research Chairs Program
- Ontario Ministry of Health and Long Term Care
The saposins are small, membrane-active proteins that exist in both soluble and lipid-bound states. Saposin A has roles in sphingolipid catabolism and transport and is required for the breakdown of galactosylceramide by beta-galactosylceramidase. In the absence of lipid, saposin A adopts a closed monomeric apo conformation typical of this family. To study a lipid-bound state of this protein, we determined the crystal structure of saposin A in the presence of detergent to 1.9 angstrom resolution. The structure reveals two chains of saposin A in an open conformation encapsulating 40 internally bound detergent molecules organized in a highly ordered bilayer-like hydrophobic core. The complex provides a high-resolution view of a discoidal lipoprotein particle in which all of the internalized acyl chains are resolved. Saposin A lipoprotein discs exhibit limited selectivity with respect to the incorporated lipid, and can solubilize phospholipids, sphingolipids, and cholesterol into discrete, monodisperse particles with mass of approximately 27 kDa. These discs may be the smallest possible lipoprotein structures that are stabilized by lipid self-assembly.
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