title: Structure of the third catalytic domain of the protein disulfide isomerase ERp46.
abstract: Protein disulfide isomerases are responsible for catalyzing the proper oxidation and isomerization of disulfide bonds of newly synthesized proteins in the endoplasmic reticulum. Here, the crystal structure of the third catalytic domain of protein disulfide isomerase ERp46 (also known as protein disulfide isomerase A5 and TXNDC5) was determined to 2.0 Å resolution. The structure shows a typical thioredoxin-like fold, but also identifies regions of high structural variability. In particular, the loop between helix α2 and strand β3 adopts strikingly different conformations among the five chains of the asymmetric unit. Cys381 and Cys388 form a structural disulfide and its absence in one of the molecules leads to dramatic conformational changes. The tryptophan residue Trp349 of this molecule inserts into the cavity formed by helices α1 and α3 of a neighbouring molecule, potentially mimicking the interactions of ERp46 with misfolded substrates.
authors.affiliation: Department of Biochemistry, Groupe de Recherche axé sur la Structure des Protéines, McGill University, 3649 Promenade Sir William Osler, Montréal, Québec H3G 0B1, Canada.
authors.forename: Irina E
authors.initials: IE
authors.lastname: Gulerez
authors.forename: Guennadi
authors.initials: G
authors.lastname: Kozlov
authors.forename: Angelika
authors.initials: A
authors.lastname: Rosenauer
authors.forename: Kalle
authors.initials: K
authors.lastname: Gehring
mesh_terms: D020134:Catalytic Domain; D006801:Humans; D008958:Models, Molecular; D019704:Protein Disulfide-Isomerases / Q000737:chemistry*
chemical_list: D019704:Protein Disulfide-Isomerases; C480743:TXNDC5 protein, human