Oxidative Folding of Proteins: Basic Principles, Cellular Regulation and Engineering
CHAPTER 3.3: Structural Insights into Disulfide Bond Formation and Protein Quality Control in the Mammalian Endoplasmic Reticulum
Published:27 Jul 2018
Special Collection: 2018 ebook collectionSeries: Chemical Biology
Masaki Okumura, Satoshi Watanabe, Kenji Inaba, 2018. "Structural Insights into Disulfide Bond Formation and Protein Quality Control in the Mammalian Endoplasmic Reticulum", Oxidative Folding of Proteins: Basic Principles, Cellular Regulation and Engineering, Matthias J Feige
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In mammalian cells, nearly one-third of proteins are targeted to the endoplasmic reticulum (ER), where they undergo disulfide bond formation, isomerization and reduction with the aid of more than 20 members of the protein disulfide isomerase (PDI) family. One likely reason for the presence of such a high number of PDI enzymes is the need to deal with a wide variety of secretory proteins under various conditions to maintain protein homeostasis in the early secretory pathway (ESP). This chapter addresses recent structural and functional studies on the diverse disulfide bond formation network constituted by PDIs and their upstream oxidases, the ERdj5-mediated disulfide reductase pathways that enhance ER-associated degradation (ERAD) and the post-ER protein quality control conducted by a pH-dependent chaperone, ERp44. The authors' comprehensive view is that PDIs with distinct functions work cooperatively and dynamically to ensure protein quality control in the ESP.