Structural highlights
Disease
SCRB2_HUMAN Unverricht-Lundborg disease;Gaucher disease type 1;Action myoclonus - renal failure syndrome. The disease is caused by mutations affecting the gene represented in this entry. Genetic variants in SCARB2 can act as modifier of the phenotypic expression and severity of Gaucher disease.
Function
SCRB2_HUMAN Acts as a lysosomal receptor for glucosylceramidase (GBA) targeting.[1]
Publication Abstract from PubMed
The integral membrane protein LIMP-2 has been a paradigm for mannose 6-phosphate receptor (MPR) independent lysosomal targeting, binding to beta-glucocerebrosidase (beta-GCase) and directing it to the lysosome, before dissociating in the late-endosomal/lysosomal compartments. Here we report structural results illuminating how LIMP-2 binds and releases beta-GCase according to changes in pH, via a histidine trigger, and suggesting that LIMP-2 localizes the ceramide portion of the substrate adjacent to the beta-GCase catalytic site. Remarkably, we find that LIMP-2 bears P-Man9GlcNAc2 covalently attached to residue N325, and that it binds MPR, via mannose 6-phosphate, with a similar affinity to that observed between LIMP-2 and beta-GCase. The binding sites for beta-GCase and the MPR are functionally separate, so that a stable ternary complex can be formed. By fluorescence lifetime imaging microscopy, we also demonstrate that LIMP-2 interacts with MPR in living cells. These results revise the accepted view of LIMP-2-beta-GCase lysosomal targeting.
Lysosome sorting of beta-glucocerebrosidase by LIMP-2 is targeted by the mannose 6-phosphate receptor.,Zhao Y, Ren J, Padilla-Parra S, Fry EE, Stuart DI Nat Commun. 2014 Jul 14;5:4321. doi: 10.1038/ncomms5321. PMID:25027712[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Reczek D, Schwake M, Schroder J, Hughes H, Blanz J, Jin X, Brondyk W, Van Patten S, Edmunds T, Saftig P. LIMP-2 is a receptor for lysosomal mannose-6-phosphate-independent targeting of beta-glucocerebrosidase. Cell. 2007 Nov 16;131(4):770-83. PMID:18022370 doi:http://dx.doi.org/10.1016/j.cell.2007.10.018
- ↑ Zhao Y, Ren J, Padilla-Parra S, Fry EE, Stuart DI. Lysosome sorting of beta-glucocerebrosidase by LIMP-2 is targeted by the mannose 6-phosphate receptor. Nat Commun. 2014 Jul 14;5:4321. doi: 10.1038/ncomms5321. PMID:25027712 doi:http://dx.doi.org/10.1038/ncomms5321
