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. J Biol Chem 2013 Jun 07;288(23):16460-16475
Date
04/24/2013Pubmed ID
23609449Pubmed Central ID
PMC3675582DOI
10.1074/jbc.M113.450239Scopus ID
2-s2.0-84878756888 (requires institutional sign-in at Scopus site) 26 CitationsAbstract
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.
Author List
Olson LJ, Orsi R, Alculumbre SG, Peterson FC, Stigliano ID, Parodi AJ, D'Alessio C, Dahms NMAuthors
Nancy M. Dahms PhD Professor in the Biochemistry department at Medical College of WisconsinLinda J. Olson PhD Assistant Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Francis C. Peterson PhD Professor in the Biochemistry department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Crystallography, X-RayEndoplasmic Reticulum
Glycoproteins
Mannose
Protein Folding
Protein Structure, Secondary
Protein Structure, Tertiary
Schizosaccharomyces
Schizosaccharomyces pombe Proteins
alpha-Glucosidases