In a recent article in Nature Communications, Janet Deane (Cambridge Institute for Medical Research) has revealed the crystal structure of a lysosomal enzyme complex that is essential for glycosphingolipid processing and is implicated in neurodegeneration.
Sphingolipids are both essential membrane components and bioactive metabolites that regulate critical cell functions. Defects in sphingolipid metabolism underlie a range of diseases, including lysosomal storage diseases, and are implicated in a number of cancers. The Deane lab focuses on the glycosphingolipid galactocerebroside — the primary lipid component of the myelin sheath that insulates axons — and its degradation by the hydrolase GALC (β-galactocerebrosidase). Mutations in GALC lead to the severe neurodegenerative disorder, Krabbe disease. In their new study, the Deane lab have determined the active complex of GALC bound to the saposin SapA, and have provided new understanding of how glycosphingolipids are bound by SapA and presented to the active site of GALC for catabolic processing.