5hqp
From Proteopedia
Crystal structure of the ERp44-peroxiredoxin 4 complex
Structural highlights
Function[PRDX4_HUMAN] Probably involved in redox regulation of the cell. Regulates the activation of NF-kappa-B in the cytosol by a modulation of I-kappa-B-alpha phosphorylation.[1] [ERP44_HUMAN] Mediates thiol-dependent retention in the early secretory pathway, forming mixed disulfides with substrate proteins through its conserved CRFS motif. Inhibits the calcium channel activity of ITPR1. May have a role in the control of oxidative protein folding in the endoplasmic reticulum. Required to retain ERO1L and ERO1LB in the endoplasmic reticulum.[2] [3] Publication Abstract from PubMedERp44 controls the localization and transport of diverse proteins in the early secretory pathway. The mechanisms that allow client recognition and the source of the oxidative power for forming intermolecular disulfides are as yet unknown. Here we present the structure of ERp44 bound to a client, peroxiredoxin 4. Our data reveal that ERp44 binds the oxidized form of peroxiredoxin 4 via thiol-disulfide interchange reactions. The structure explains the redox-dependent recognition and characterizes the essential non-covalent interactions at the interface. The ERp44-Prx4 covalent complexes can be reduced by glutathione and protein disulfide isomerase family members in the ER, allowing the two components to recycle. This work provides insights into the mechanisms of thiol-mediated protein retention and indicates the key roles of ERp44 in this biochemical cycle to optimize oxidative folding and redox homeostasis. Crystal Structure of the ERp44-Peroxiredoxin 4 Complex Reveals the Molecular Mechanisms of Thiol-Mediated Protein Retention.,Yang K, Li DF, Wang X, Liang J, Sitia R, Wang CC, Wang X Structure. 2016 Oct 4;24(10):1755-1765. doi: 10.1016/j.str.2016.08.002. Epub 2016, Sep 15. PMID:27642162[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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