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A critical histidine residue within LIMP-2 mediates pH sensitive binding to its ligand β-glucocerebrosidase.
- Source :
-
Traffic (Copenhagen, Denmark) [Traffic] 2012 Aug; Vol. 13 (8), pp. 1113-23. Date of Electronic Publication: 2012 May 15. - Publication Year :
- 2012
-
Abstract
- The lysosomal membrane protein type 2 is a novel identified lysosomal sorting receptor for β-glucocerebrosidase (GC). Mutations in both genes underlie human pathologies causing action myoclonus-renal failure syndrome (AMRF) and Gaucher disease (GD), respectively. We now demonstrate that the lumenal acidification mediated by the vacuolar (H(+) )-ATPase triggers the dissociation of LIMP-2 and GC in late endosomal/lysosomal compartments. Moreover, we identified a single histidine residue in LIMP-2 that is necessary for LIMP-2 and GC binding. This residue is in close proximity to a proposed coiled-coil domain, which determines the binding to GC and may function as a critical pH sensor.<br /> (© 2012 John Wiley & Sons A/S.)
- Subjects :
- Amino Acid Sequence
Animals
COS Cells
Cells, Cultured
Chlorocebus aethiops
Codon, Nonsense
Endosomes enzymology
Endosomes metabolism
Enzyme Inhibitors pharmacology
Fibroblasts metabolism
HeLa Cells
Humans
Hydrogen-Ion Concentration
Lysosomal Membrane Proteins metabolism
Lysosomes enzymology
Lysosomes metabolism
Macrolides pharmacology
Mice
Molecular Sequence Data
Mutation, Missense
Myoclonic Epilepsies, Progressive genetics
Protein Binding genetics
Receptors, Scavenger metabolism
Vacuolar Proton-Translocating ATPases antagonists & inhibitors
Vacuolar Proton-Translocating ATPases metabolism
Glucosylceramidase metabolism
Histidine chemistry
Lysosomal Membrane Proteins chemistry
Lysosomal Membrane Proteins genetics
Receptors, Scavenger chemistry
Receptors, Scavenger genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1600-0854
- Volume :
- 13
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Traffic (Copenhagen, Denmark)
- Publication Type :
- Academic Journal
- Accession number :
- 22537104
- Full Text :
- https://doi.org/10.1111/j.1600-0854.2012.01372.x