The mechanism of glycosphingolipid degradation revealed by a GALC-SapA complex structure

Chris H. Hill, Georgia M. Cook, Samantha J. Spratley, Stuart Fawke, Stephen C. Graham and Janet E. Deane ()
Additional contact information
Chris H. Hill: University of Cambridge
Georgia M. Cook: University of Cambridge
Samantha J. Spratley: University of Cambridge
Stuart Fawke: University of Cambridge
Stephen C. Graham: University of Cambridge
Janet E. Deane: University of Cambridge

Nature Communications, 2018, vol. 9, issue 1, 1-9

Abstract: Abstract Sphingolipids are essential components of cellular membranes and defects in their synthesis or degradation cause severe human diseases. The efficient degradation of sphingolipids in the lysosome requires lipid-binding saposin proteins and hydrolytic enzymes. The glycosphingolipid galactocerebroside is the primary lipid component of the myelin sheath and is degraded by the hydrolase β-galactocerebrosidase (GALC). This enzyme requires the saposin SapA for lipid processing and defects in either of these proteins causes a severe neurodegenerative disorder, Krabbe disease. Here we present the structure of a glycosphingolipid-processing complex, revealing how SapA and GALC form a heterotetramer with an open channel connecting the enzyme active site to the SapA hydrophobic cavity. This structure defines how a soluble hydrolase can cleave the polar glycosyl headgroups of these essential lipids from their hydrophobic ceramide tails. Furthermore, the molecular details of this interaction provide an illustration for how specificity of saposin binding to hydrolases is encoded.

Date: 2018
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-017-02361-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02361-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-017-02361-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().