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Saposin C protects glucocerebrosidase against ?-synuclein inhibition.

ABSTRACT: Mutations in GBA1, the gene for glucocerebrosidase (GCase), are genetic risk factors for Parkinson disease (PD). ?-Synuclein (?-Syn), a protein implicated in PD, interacts with GCase and efficiently inhibits enzyme activity. GCase deficiency causes the lysosomal storage disorder Gaucher disease (GD). We show that saposin C (Sap C), a protein vital for GCase activity in vivo, protects GCase against ?-syn inhibition. Using nuclear magnetic resonance spectroscopy, site-specific fluorescence, and Förster energy transfer probes, Sap C was observed to displace ?-syn from GCase in solution and on lipid vesicles. Our results suggest that Sap C might play a crucial role in GD-related PD.

SUBMITTER: Yap TL

PROVIDER: S-EPMC3833811 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Saposin C protects glucocerebrosidase against α-synuclein inhibition.

Yap Thai Leong TL Gruschus James M JM Velayati Arash A Sidransky Ellen E Lee Jennifer C JC

Biochemistry 20131001 41

Mutations in GBA1, the gene for glucocerebrosidase (GCase), are genetic risk factors for Parkinson disease (PD). α-Synuclein (α-Syn), a protein implicated in PD, interacts with GCase and efficiently inhibits enzyme activity. GCase deficiency causes the lysosomal storage disorder Gaucher disease (GD). We show that saposin C (Sap C), a protein vital for GCase activity in vivo, protects GCase against α-syn inhibition. Using nuclear magnetic resonance spectroscopy, site-specific fluorescence, and Fö ...[more]

PMID: 24070323

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