Zhening Zhang, Wenguang G Liang, Lucas J Bailey, Yong Zi Tan, Hui Wei, Andrew Wang, Mara Farcasanu, Virgil A Woods, Lauren A McCord, David Lee, Weifeng Shang, Rebecca Deprez-Poulain, Benoit Deprez, David R Liu, Akiko Koide, Shohei Koide, Anthony A Kossiakoff, Sheng Li, Bridget Carragher, Clinton S Potter, Wei-Jen Tang
Insulin degrading enzyme (IDE) plays key roles in degrading peptides vital in type 2 diabetes, Alzheimer's, inflammation, and other human diseases. However, the process through which IDE recognizes peptides that tend to form amyloid fibrils remained unsolved. We used cryoEM to understand both the apo- and insulin-bound dimeric IDE states, revealing that IDE displays a large opening between the homologous ~55 kDa N- and C-terminal halves to allow selective substrate capture based on size and charge complementarity...
March 29, 2018: ELife