How do PDI family member proteins act on unfolded/misfolded proteins to ensure protein quality control in the early secretory pathway?
Speaker: Kenji Inaba, Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Japan
Endoplasmic reticulum (ER) is the essential organelle that has evolved stringent quality control systems for secretory and cell surface membrane proteins. Formation, isomerization and reduction of disulfide bonds play important roles in maintaining protein homeostasis in this organelle. Although more than 20 kinds of protein disulfide isomerase family members have so far been identified in mammalian cells, their physiological functions are not fully understood. Our crystallographic and single-molecule observation studies have provided important insights into how the PDI family members act on unfolded/misofolded proteins to promote their oxidative folding and ER-associated degradation. The key mechanistic feature of the PDI family members is that they undergo significant dynamics in a redox- and substrate-dependent manner to fulfill their unique functions with high efficiency.