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

JOURNAL OF BIOLOGICAL CHEMISTRY

AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

Lugar: Bethesda, Maryland; Año: 2013 vol. 288 p. 16460 - 16475

0021-9258

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 (ER). GII removes the two innermost glucose residues from the Glc3Man9GlcNAc2 transferred to nascent proteins and also the glucose added by the UDP-Glc:glycoprotein glucosyltransferase. GII is composed of a catalytic GII alpha subunit and a regulatory GIIbeta subunit. GIIbeta participates in GII alpha´s ER localization and mediates in vivo enhancement of N-glycan trimming by GII through its C-terminal 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 accomodates a single mannose residue. In addition, we identified a conserved residue outside the binding pocket (Trp-409) present in GIIbeta but not in other MRH´s that influences GII glucose trimming activity