Open AccessStructure of the third catalytic domain of the protein disulfide isomerase ERp46
Author(s) -
Gulerez Irina E.,
Kozlov Guennadi,
Rosenauer Angelika,
Gehring Kalle
Publication year - 2012
Publication title -
acta crystallographica section f
Language(s) - English
Resource type - Journals
ISSN - 1744-3091
DOI - 10.1107/s1744309112005866
Subject(s) - protein disulfide isomerase , isomerase , chemistry , residue (chemistry) , molecule , isomerization , protein folding , helix (gastropod) , foldase , crystallography , stereochemistry , protein structure , thioredoxin , endoplasmic reticulum , catalysis , biochemistry , enzyme , biology , organic chemistry , ecology , gene , escherichia coli , groel , snail
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.