title: Peptide binding by catalytic domains of the protein disulfide isomerase-related protein ERp46.
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.
authors: Max Planck Research Unit for Enzymology of Protein Folding, Weinbergweg 22, 06120 Halle (Saale), Germany.
authors: Andreas
authors: A
authors: Funkner
authors: Christoph
authors: C
authors: Parthier
authors: Mike
authors: M
authors: Schutkowski
authors: Johnny
authors: J
authors: Zerweck
authors: Hauke
authors: H
authors: Lilie
authors: Natalya
authors: N
authors: Gyrych
authors: Gunter
authors: G
authors: Fischer
authors: Milton T
authors: MT
authors: Stubbs
authors: David M
authors: DM
authors: Ferrari
mesh_terms: D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D019704:Protein Disulfide-Isomerases / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D019704:Protein Disulfide-Isomerases; C480743:TXNDC5 protein, human