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 |
16460-16475
|
Published |
2013-6-7
|
DOI |
10.1074/jbc.M113.450239
|
PII |
S0021-9258(20)53655-7
|
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
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
Resource |
DNA material |
S. pombe entry SpEnt26D11 (SPW010483). |