3UJ1

Crystal structure of the third thioredoxin domain of human ERp46

Summary for 3UJ1

• Entry DOI: 10.2210/pdb3uj1/pdb
• Descriptor: Thioredoxin domain-containing protein 5 (2 entities in total)
• Functional Keywords: thioredoxin fold, protein disulfide isomerase, protein folding, endoplasmic reticulum, substrate binding, chaperone
• Biological source: Homo sapiens (human)
• Cellular location: Endoplasmic reticulum lumen (By similarity): Q8NBS9
• Total number of polymer chains: 1
• Total formula weight: 12268.98

Authors

Parthier, C.,Funkner, A.,Ferrari, D.M.,Stubbs, M.T. (deposition date: 2011-11-07, release date: 2012-11-07, Last modification date: 2024-11-06)

Primary citation

Funkner, A.,Parthier, C.,Schutkowski, M.,Zerweck, J.,Lilie, H.,Gyrych, N.,Fischer, G.,Stubbs, M.T.,Ferrari, D.M.
Peptide Binding by Catalytic Domains of the Protein Disulfide Isomerase-Related Protein ERp46.
J.Mol.Biol., 425:1340-1362, 2013

PubMed Abstract: The protein disulfide isomerase (PDI) family member ERp46/endoPDI/thioredoxin domain-containing protein 5 is preferentially expressed in a limited number of tissues, where it may function as a survival factor for nitrosative stress in vivo. It is involved in insulin production as well as in adiponectin signaling and interacts specifically with the redox-regulatory endoplasmic reticulum proteins endoplasmic oxidoreductin 1α (Ero1α) and peroxiredoxin-4. Here, we show that ERp46, although lacking a PDI-like redox-inactive b'-thioredoxin domain with its hydrophobic substrate binding site, is able to bind to a large pool of peptides containing aromatic and basic residues via all three of its catalytic domains (a(0), a and a'), though the a(0) domain may contain the primary binding site. ERp46, which shows relatively higher activity as a disulfide-reductase than as an oxidase/isomerase in vitro compared to PDI and ERp57, possesses chaperone activity in vivo, a property also shared by the C-terminal a' domain. A crystal structure of the a' domain is also presented, offering a view of possible substrate binding sites within catalytic domains of PDI proteins.

PubMed: 23376096
DOI: 10.1016/j.jmb.2013.01.029

Experimental method

X-RAY DIFFRACTION (2.651 Å)