Peptide Binding by Catalytic Domains of the Protein Disulfide Isomerase-Related Protein ERp46
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- 作者：Andreas Funkner1 ; &dagger ; ; Christoph Parthier2 ; &dagger ; ; christoph.parthier@biochemtech.uni-halle.de ; Mike Schutkowski2 ; mike.schutkowski@biochemtech.uni-halle.de ; Johnny Zerweck3 ; Hauke Lilie2 ; hauke.lilie@biochemtech.uni-halle.de ; Natalya Gyrych1 ; Gunter Fischer1 ; fischer@enzyme-halle.mpg.de ; Milton T. Stubbs2 ; stubbs@biochemtech.uni-halle.de ; David M. Ferrari1 ; ferrari@enzyme-halle.mpg.de
- 关键词：EDTA ; ethylenediaminetetraacetic acid ; ER ; endoplasmic reticulum ; GST ; glutathione S-transferase ; PDB ; Protein Data Bank ; PDI ; protein disulfide isomerase ; Trx ; thioredoxin ; WT ; wild type
- 刊名：Journal of Molecular Biology
- 出版年：2013
- 出版时间：26 April, 2013
- 年：2013
- 卷：425
- 期：8
- 页码：1340-1362
- 全文大小：2068 K
文摘
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 1¦Á (Ero1¦Á) and peroxiredoxin-4. Here, we show that ERp46, although lacking a PDI-like redox-inactive b¡ä-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 (a0, a and a¡ä), though the a0 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¡ä domain. A crystal structure of the a¡ä domain is also presented, offering a view of possible substrate binding sites within catalytic domains of PDI proteins.