2lvx

Publication Abstract from PubMed

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 GIIalpha subunit and a regulatory GIIbeta subunit. GIIbeta participates in the endoplasmic reticulum localization of GIIalpha and mediates in vivo enhancement of N-glycan trimming by GII through its C-terminal MRH domain. We determined the structure of a functional GIIbeta MRH domain by NMR spectroscopy. It adopts a beta-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 GIIbeta but not in other MRHs that influences GII glucose trimming activity.

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.,Olson LJ, Orsi R, Alculumbre SG, Peterson FC, Stigliano ID, Parodi AJ, D'Alessio C, Dahms NM J Biol Chem. 2013 Jun 7;288(23):16460-75. doi: 10.1074/jbc.M113.450239. Epub 2013, Apr 22. PMID:23609449^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.