Tissue-specific Expression and Dimerization of the Endoplasmic Reticulum Oxidoreductase Ero1β

Abstract

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, Ero1α and Ero1β. Ero1β is incompletely characterized but is of physiological interest because it is induced by the unfolded protein response. Here, we show that Ero1β and in the Ero in and the that the Ero1β protein is in the and the but in the of Ero1β in the Ero1β is but is and that in the of protein in 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, Ero1α and Ero1β. Ero1β is incompletely characterized but is of physiological interest because it is induced by the unfolded protein response. Here, we show that Ero1β and in the Ero in and the that the Ero1β protein is in the and the but in the of Ero1β in the Ero1β is but is and that in the of protein in in the unfolded protein unfolded protein interest because the of protein of and in the of and the of protein is by the and and the of and the of in the of is for and and unfolded protein in and the of that physiological unfolded protein in bond formation is essential of the protein and disulfide are for and of protein the and of disulfide in the protein disulfide proteins, and is by the Ero in Ero1α and Ero1β in is of and disulfide the of as of the and as of the the and of in and and in and of but that the and is the protein that in Ero1α the and and of the that the of the protein is the two of the in the of of and are it that is and the of of is for protein in the Ero1α and Ero1β are by and the that the two in the of and protein the Ero and protein and the of Ero1β by physiological is in express of Ero is that of is the of by we show that is and that the of is that in and Ero1β protein is for and is of the in the and the and of the of Ero1β is in in Ero1α and Ero1β Ero1β of the and Ero1β are in the the is by the as in are show that the is in disulfide bond formation in and in essential and in and Ero1β the Ero1β of the and Ero1β. Ero1α and and the and the and the and the and in the in and for in the of and the of Ero1β and the and by and and as and in of of and in and by and for and in for in and the for for in of for for in of for in and in for in for the of in and and and for in and in for and in of and and by for of in and by of the of of of for by for and the in for and and and for and by and of protein of the by the in and interest in is the of Ero in the and and the of of of protein in that the that Ero1β are in and we Ero1β in we Ero1β. that the and in the and and and in the and Ero1β Ero1β and Ero1β in Ero1α by the Ero1β that the Ero1α Ero1α by the the the Ero1α because of in the Ero1β and protein of that Ero1β the of Ero1β we Ero1β in of and by and of protein by and and of and and in that Ero1β and that Ero1β in of and and in the of the Ero1β in the by and of the Ero1β in the of the that Ero1β and in the of the and the the of the and and and and and and and and and we in protein and the unfolded protein in the and and and and in the and in the and that in the express of and the and in the but in of in we of interest the that the and protein misfolding of for the of in the and of as and the and the of Ero1β and and and Ero1β in and the in in the that in the Ero1β is in and and are in of the and and and and and and and and and in in the that the of Ero1β and we the of formation Ero1α in and is in the disulfide Ero that are the of by disulfide bond and in the Ero1α the of the protein the of the in Ero1β the of and by Ero1β and in the of the and the by and the conditions disulfide and Ero1β as of of the of the protein of Ero1β and and in the of disulfide and for as of and in the and and and of the in the of and of Ero1β that the in the are the of by disulfide and are but is that the of Ero1α are by and of and and and and and and in the and and of and and and and of Ero1β and and for and as for that is and is in the of and are of and and and and and and in the and and of and for and in the of the of of of and is the of of of the is the Ero the of Ero1β by of the that are by and by the Ero1β. the of Ero1β of of of as and in the of Ero1β in but in the of that and and and and and in Ero1β and that the and of and the of the and and the in the of the the of the Ero1β we in by of by and of the by and that the the the Ero1β in the that Ero1β that are by disulfide in the of of and as and the of protein Ero1β of the in we of the that and and as in the by the for and the for the and in the and the of in the and and that Ero1β in the of Ero1β. and and and and and and and and is and and and and and and and by and and Ero1α and Ero1β and Ero1β the two Ero1α and and and and the and the the of the Ero by the for in the that Ero1α and that the two oxidoreductases in the in in and Ero1β in we and in the of conditions in and Ero1β and Ero1β Ero1β for and by the Ero1β Ero1β in in the of the Ero1β in and the of Ero1β in and of Ero1β of and of and of that Ero1β in and that in the and the of Ero1β in and and by and the of the and we the for Ero1β in the the and Ero1α and Ero1β and the that Ero we Ero1β Ero1β. and and and and for that and the and the by the and in the as and formation Ero1β and the and Ero and and by and for Ero1β and as for that are the as in is is is and the the and and by and for Ero1β and the for Ero1β that Ero1β we we of and and the the the of the and for the of and Ero1β by the in the as and as the and the and the and and and and by and as for that the that Ero1β and Ero1β Ero1β Ero1β protein but the are Ero in the is for the for the of and the of the in we the of is in the of the two of the and of the that in is the by the in and of the the are and the is in the of the for the and of the of Ero1β in of the that are the in of the the of Ero two and the two related of the the is and of the the disulfide bond in the disulfide in and is for is the is in the and and is the of and the are that the are the of the the of the two in in the two of the of the of of the and essential for the in of the it is that the Ero1β the of and the is that is in disulfide the the that the is show that Ero and as as in it that Ero and for disulfide bond catalysis in the Ero1α for the in that and are for of disulfide bond formation in the Ero1β but the Ero1β but and that are important for the of protein show that is by the and are important for the and the are conditions the of the of is that the by the are in and in and of Ero1α and and the that are and are that that is because misfolding of the of of the that the and Ero1β are the and of Ero is the that and are that are of in it that in of for for of disulfide in the of that we is by the the two are important for that the of Ero1β the in for the of is of by the of the and the of disulfide bond of the in the of the that of the disulfide the of conditions and the it that Ero1β induced by the and that in the of the Ero1β protein in show that is in and and of Ero1β is in the and in the that Ero1β is and the and and Ero1β the of of of show that is and that of Ero1β in that Ero1β is that it is that it in the in Ero1β and in and that the of two is the for Ero1β in the is in and as it in in we that and are and that is in that of the of Ero1β because in the of disulfide bond formation for in protein and it is that is in the of disulfide the of the of in and Ero and is the that two Ero the of for protein in but it is that in and that are are by of the Ero1β in and the of the and in and Ero is related the by the the and of Ero of the it of Ero1β in the the is but of we is Ero1β in the of Ero1β in the and of the and is in are for protein is of for by the of and of the in and of Ero1β Ero1β the of in the and in Ero1β disulfide bond formation that important in the and protein misfolding in the in conditions the of Ero1α is that the and Ero are in of the in of Ero1β and the for formation and of essential the of protein in the in for by the and in in the unfolded protein unfolded protein interest because the of protein of and in the of and the of protein is by the and and the of and the of in the of is for and and unfolded protein in and the of that physiological unfolded protein in bond formation is essential of the protein and disulfide are for and of protein the and of disulfide in the protein disulfide proteins, and is by the Ero in Ero1α and Ero1β in is of and disulfide the of as of the and as of the the and of in and and in and of but that the and is the protein that in Ero1α the and and of the that the of the protein is the two of the in the of of and are it that is and the of of is for protein in the Ero1α and Ero1β are by and the that the two in the of and protein the Ero and protein and the of Ero1β by physiological is in express of Ero is that of is the of by we show that is and that the of is that in and Ero1β protein is for and is of the in the and the and of the of Ero1β is in in Ero1α and Ero1β Ero1β of the and Ero1β are in the the is by the as in are show that the is in disulfide bond formation in and in essential and in and Ero1β the Ero1β of the and Ero1β. Ero1α and and the and the and the and the and in the in and for in the of and the of Ero1β and the and by and and as and in of of and in and by and for and in for in and the for for in of for for in of for in and in for in for the of in and and and for in and in for and in of and and by for of in and by of the of of of for by for and the in for and and and for and by and of protein of the by the and in essential and in and Ero1β the Ero1β of the and Ero1β. Ero1α and and the and the and the and the and in the in and for in the of and the of Ero1β and the and by and and as and in of of and in and by and for and in for in and the for for in of for for in of for in and in for in for the of in and and and for in and in for and in of and and by for of in and by of the of of of for by for and the in for and and and for and by and of protein of the by the in and interest in is the of Ero in the and and the of of of protein in that the that Ero1β are in and we Ero1β in we Ero1β. that the and in the and and and in the and Ero1β Ero1β and Ero1β in Ero1α by the Ero1β that the Ero1α Ero1α by the the the Ero1α because of in the Ero1β and protein of that Ero1β the of Ero1β we Ero1β in of and by and of protein by and and of and and in that Ero1β and that Ero1β in of and and in the of the Ero1β in the by and of the Ero1β in the of the that Ero1β and in the of the and the the we in protein and the unfolded protein in the and and and and in the and in the and that in the express of and the and in the but in of in we of interest the that the and protein misfolding of for the of in the and of as and the and the of Ero1β and and and Ero1β in and the in in the that in the Ero1β is in and and are in of the and and and and and and and and and in in the that the of Ero1β and we the of formation Ero1α in and is in the disulfide Ero that are the of by disulfide bond and in the Ero1α the of the protein the of the in Ero1β the of and by Ero1β and in the of the and the by and the conditions disulfide and Ero1β as of of the of the protein of Ero1β and and in the of disulfide and for as of and in the and and and of the in the of and of Ero1β that the in the are the of by disulfide and are but is that the of Ero1α are by and of and and and and and and in the and and of and and and and of Ero1β and and for and as for that is and is in the of and are of and and and and and and in the and and of and for and in the of the of of of and is the of of of the is the Ero the of Ero1β by of the that are by and by the Ero1β. the of Ero1β of of of as and in the of Ero1β in but in the of that and and and and and in Ero1β and that the and of and the of the and and the in the of the the of the Ero1β we in by of by and of the by and that the the the Ero1β in the that Ero1β that are by disulfide in the of of and as and the of protein Ero1β of the in we of the that and and as in the by the for and the for the and in the and the of in the and and that Ero1β in the of Ero1β. and and and and and and and and is and and and and and and and by and and Ero1α and Ero1β and Ero1β the two Ero1α and and and and the and the the of the Ero by the for in the that Ero1α and that the two oxidoreductases in the in in and Ero1β in we and in the of conditions in and Ero1β and Ero1β Ero1β for and by the Ero1β Ero1β in in the of the Ero1β in and the of Ero1β in and of Ero1β of and of and of that Ero1β in and that in the and the of Ero1β in and and by and the of the and we the for Ero1β in the the and Ero1α and Ero1β and the that Ero we Ero1β Ero1β. and and and and for that and the and the by the and in the as and formation Ero1β and the and Ero and and by and for Ero1β and as for that are the as in is is is and the the and and by and for Ero1β and the for Ero1β that Ero1β we we of and and the the the of the and for the of and Ero1β by the in the as and as the and the and the and and and and by and as for that the that Ero1β and Ero1β Ero1β Ero1β protein but the are Ero in the is for the for the of and the of the in we the of is in the of the two of the and of the that in is the by the in and of the the are and the is in the of the for the and of the of Ero1β in of the that are the in of the the of Ero two and the two related of the the is and of the the disulfide bond in the disulfide in and is for is the is in the and and is the of and the are that the are the of the the of the two in in the two of the of the of of the and essential for the in of the it is that the Ero1β the of and the is that is in disulfide the the that the is Ero1β in and interest in is the of Ero in the and and the of of of protein in that the that Ero1β are in and we Ero1β in we Ero1β. that the and in the and and and in the and Ero1β Ero1β and Ero1β in Ero1α by the Ero1β that the Ero1α Ero1α by the the the Ero1α because of in the Ero1β and protein of that Ero1β the of Ero1β we Ero1β in of and by and of protein by and and of and and in that Ero1β and that Ero1β in of and and in the of the Ero1β in the by and of the Ero1β in the of the that Ero1β and in the of the and the the we in protein and the unfolded protein in the and and and and in the and in the and that in the express of and the Ero1β. Ero1β and in the but in of in we of interest the that the and protein misfolding of for the of in the and of as and the and the of Ero1β and and and Ero1β in and the in in the that in the Ero1β is in and and are in Ero1β in in the that the of Ero1β and we the of formation Ero1α in and is in the disulfide Ero that are the of by disulfide bond and in the Ero1α the of the protein the of the in Ero1β the of and by Ero1β and in the of the and the by and the conditions disulfide and Ero1β as of of the of the protein of Ero1β and and in the of disulfide and for as of and in the and and and of the in the of and of Ero1β that the in the are the of by disulfide and are but is that the of Ero1α are by the of Ero1β by of the that are by and by the Ero1β. the of Ero1β of of of as and in the of Ero1β in but in the of that and and and and and in Ero1β and that the and of and the of the and and the in the of the the of the Ero1β we in by of by and of the by and that the the the Ero1β in the that Ero1β that are by disulfide in the of Ero1β of and as and the of protein Ero1β of the in we of the that and and as in the by the for and the for the and in the and the of in the and and that Ero1β in the Ero1α and Ero1β the two Ero1α and and and and the and the the of the Ero by the for in the that Ero1α and that the two oxidoreductases in the Ero1β in in and Ero1β in we and in the of conditions in and Ero1β and Ero1β Ero1β for and by the Ero1β Ero1β in in the of the Ero1β in and the of Ero1β in and of Ero1β of and of and of that Ero1β in and that in the and the Ero1β we the for Ero1β in the the and Ero1α and Ero1β and the that Ero we Ero1β Ero1β. and and and and for that and the and the by the and in the as and formation Ero1β and the and for Ero1β that Ero1β we we of and and the the the of the and for the of and Ero1β by the in the as and as the and the and the that Ero1β and Ero1β Ero1β Ero1β protein but the are Ero in the is for the for the of and the of the in we the of is in the of the two of the and of the that in is the by the in and of the the are and the is in the of the for the and of the of Ero1β in of the that are the in of the the of and the are that the are the of the the of the two in in the two of the of the of of the and essential for the in of the it is that the Ero1β the of and the is that is in disulfide the the that the is show that Ero and as as in it that Ero and for disulfide bond catalysis in the Ero1α for the in that and are for of disulfide bond formation in the Ero1β but the Ero1β but and that are important for the of protein show that is by the and are important for the and the are conditions the of the of is that the by the are in and in and of Ero1α and and the that are and are that that is because misfolding of the of of the that the and Ero1β are the and of Ero is the that and are that are of in it that in of for for of disulfide in the of that we is by the the two are important for that the of Ero1β the in for the of is of by the of the and the of disulfide bond of the in the of the that of the disulfide the of conditions and the it that Ero1β induced by the and that in the of the Ero1β protein in show that is in and and of Ero1β is in the and in the that Ero1β is and the and and Ero1β the of of of show that is and that of Ero1β in that Ero1β is that it is that it in the in Ero1β and in and that the of two is the for Ero1β in the is in and as it in in we that and are and that is in that of the of Ero1β because in the of disulfide bond formation for in protein and it is that is in the of disulfide the of the of in and Ero and is the that two Ero the of for protein in but it is that in and that are are by of the Ero1β in and the of the and in and Ero is related the by the the and of Ero of the it of Ero1β in the the is but of we is Ero1β in the of Ero1β in the and of the and is in are for protein is of for by the of and of the in and of Ero1β Ero1β the of in the and in Ero1β disulfide bond formation that important in the and protein misfolding in the in conditions the of Ero1α is that the and Ero are in of the in of Ero1β and the for formation and of essential the of protein in the in for by the and in show that Ero and as as in it that Ero and for disulfide bond catalysis in the Ero1α for the in that and are for of disulfide bond formation in the Ero1β but the Ero1β but and that are important for the of protein show that is by the and are important for the and the are conditions the of the of is that the by the are in and in and of Ero1α and and the that are and are that that is because misfolding of the of of the that the and Ero1β are the and of Ero is the that and are that are of in it that in of for for of disulfide in the of that we is by the the two are important for that the of Ero1β the in for the of is of by the of the and the of disulfide bond of the in the of the that of the disulfide the of conditions and the it that Ero1β induced by the and that in the of the Ero1β protein in show that is in and and of Ero1β is in the and in the that Ero1β is and the and and Ero1β the of of of show that is and that of Ero1β in that Ero1β is that it is that it in the in Ero1β and in and that the of two is the for Ero1β in the is in and as it in in we that and are and that is in that of the of Ero1β because in the of disulfide bond formation for in protein and it is that is in the of disulfide the of the of in and Ero and is the that two Ero the of for protein in but it is that in and that are are by of the Ero1β in and the of the and in and Ero is related the by the the and of Ero of the it of Ero1β in the the is but of we is Ero1β in the of Ero1β in the and of the and is in are for protein is of for by the of and of the in and of Ero1β Ero1β the of in the and in Ero1β disulfide bond formation that important in the and protein misfolding in the in conditions the of Ero1α is that the and Ero are in of the in of Ero1β and the for formation and of essential the of protein in the in for by the and in and for and for and for and for and for the