Tissue-specific expression and dimerization of the endoplasmic reticulum oxidoreductase Ero1beta.
Endoplasmic reticulum oxidoreductases (Eros) are essential for the formation of disulfide bonds. Understanding disulfide bond catalysis in mammals is important because of the involvement of protein misfolding in conditions such as diabetes, arthritis, cancer, and aging. Mammals express two related Ero proteins, Ero1alpha and Ero1beta. Ero1beta is incompletely characterized but is of physiological interest because it is induced by the unfolded protein response. Here, we show that Ero1beta can form homodimers and mixed heterodimers with Ero1alpha, in addition to Ero-PDI dimers. Ero-Ero dimers require the Ero active site, occur in vivo, and can be modeled onto the Ero1p crystal structure. Our data indicate that the Ero1beta protein is constitutively strongly expressed in the stomach and the pancreas, but in a cell-specific fashion. In the stomach, selective expression of Ero1beta occurs in the enzyme-producing chief cells. In pancreatic islets, Ero1beta expression is high, but is inversely correlated with PDI and PDIp levels, demonstrating that cell-specific differences exist in the regulation of oxidative protein folding in vivo.
Dias-Gunasekara
Sanjika
S
School of Biological and Biomedical Sciences, University of Durham, England.
Gubbens
Jacob
J
van Lith
Marcel
M
Dunne
Christine
C
Williams
J A Gareth
JA
Kataky
Ritu
R
Scoones
David
D
Lapthorn
Adrian
A
Bulleid
Neil J
NJ
Benham
Adam M
AM
D001665:Binding Sites; D015153:Blotting, Western; D002384:Catalysis; D045744:Cell Line, Tumor; D002850:Chromatography, Gel; D018360:Crystallography, X-Ray; D019281:Dimerization; D004220:Disulfides / Q000737:chemistry; D004591:Electrophoresis, Polyacrylamide Gel; D004721:Endoplasmic Reticulum / Q000201:enzymology*; D005753:Gastric Mucosa / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D007515:Islets of Langerhans / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000737:chemistry*; D008958:Models, Molecular; D009154:Mutation; D010084:Oxidation-Reduction; D050862:Oxidoreductases Acting on Sulfur Group Donors; D010100:Oxygen / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism; D011489:Protein Denaturation; D017510:Protein Folding; D014018:Tissue Distribution; D014162:Transfection
D004220:Disulfides; D008562:Membrane Glycoproteins; D050862:Oxidoreductases Acting on Sulfur Group Donors; C485767:ERO1B protein, human; D010100:Oxygen