RRC ID 30216
Author Olson LJ, Orsi R, Alculumbre SG, Peterson FC, Stigliano ID, Parodi AJ, D'Alessio C, Dahms NM.
Title Structure of the lectin mannose 6-phosphate receptor homology (MRH) domain of glucosidase II, an enzyme that regulates glycoprotein folding quality control in the endoplasmic reticulum.
Journal J Biol Chem
Abstract Here we report for the first time the three-dimensional structure of a mannose 6-phosphate receptor homology (MRH) domain present in a protein with enzymatic activity, glucosidase II (GII). GII is involved in glycoprotein folding in the endoplasmic reticulum. GII removes the two innermost glucose residues from the Glc3Man9GlcNAc2 transferred to nascent proteins and the glucose added by UDP-Glc:glycoprotein glucosyltransferase. GII is composed of a catalytic GIIα subunit and a regulatory GIIβ subunit. GIIβ participates in the endoplasmic reticulum localization of GIIα and mediates in vivo enhancement of N-glycan trimming by GII through its C-terminal MRH domain. We determined the structure of a functional GIIβ MRH domain by NMR spectroscopy. It adopts a β-barrel fold similar to that of other MRH domains, but its binding pocket is the most shallow known to date as it accommodates a single mannose residue. In addition, we identified a conserved residue outside the binding pocket (Trp-409) present in GIIβ but not in other MRHs that influences GII glucose trimming activity.
Volume 288(23)
Pages 16460-75
Published 2013-6-7
DOI 10.1074/jbc.M113.450239
PII M113.450239
PMID 23609449
PMC PMC3675582
MeSH Crystallography, X-Ray Endoplasmic Reticulum* / chemistry Endoplasmic Reticulum* / genetics Endoplasmic Reticulum* / metabolism Glycoproteins* / chemistry Glycoproteins* / genetics Glycoproteins* / metabolism Mannose / chemistry Mannose / genetics Mannose / metabolism Protein Folding* Protein Structure, Secondary Protein Structure, Tertiary Schizosaccharomyces / enzymology* Schizosaccharomyces / genetics Schizosaccharomyces pombe Proteins* / chemistry Schizosaccharomyces pombe Proteins* / genetics Schizosaccharomyces pombe Proteins* / metabolism alpha-Glucosidases* / chemistry alpha-Glucosidases* / genetics alpha-Glucosidases* / metabolism
IF 4.238
Times Cited 21
DNA material S. pombe entry SpEnt26D11 (SPW010483).