7WR7

Structure of Inhibited-EP

7WR7 の概要

• エントリーDOI: 10.2210/pdb7wr7/pdb
• EMDBエントリー: 32717
• 分子名称: Enteropeptidase non-catalytic heavy chain, Enteropeptidase catalytic light chain, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• 機能のキーワード: complex, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 57151.06

構造登録者

Yang, X.L.,Ding, Z.Y.,Huang, H.J. (登録日: 2022-01-26, 公開日: 2022-10-26, 最終更新日: 2024-10-30)

主引用文献

Yang, X.,Ding, Z.,Peng, L.,Song, Q.,Zhang, D.,Cui, F.,Xia, C.,Li, K.,Yin, H.,Li, S.,Li, Z.,Huang, H.
Cryo-EM structures reveal the activation and substrate recognition mechanism of human enteropeptidase.
Nat Commun, 13:6955-6955, 2022

PubMed Abstract: Enteropeptidase (EP) initiates intestinal digestion by proteolytically processing trypsinogen, generating catalytically active trypsin. EP dysfunction causes a series of pancreatic diseases including acute necrotizing pancreatitis. However, the molecular mechanisms of EP activation and substrate recognition remain elusive, due to the lack of structural information on the EP heavy chain. Here, we report cryo-EM structures of human EP in inactive, active, and substrate-bound states at resolutions from 2.7 to 4.9 Å. The EP heavy chain was observed to clamp the light chain with CUB2 domain for substrate recognition. The EP light chain N-terminus induced a rearrangement of surface-loops from inactive to active conformations, resulting in activated EP. The heavy chain then served as a hinge for light-chain conformational changes to recruit and subsequently cleave substrate. Our study provides structural insights into rearrangements of EP surface-loops and heavy chain dynamics in the EP catalytic cycle, advancing our understanding of EP-associated pancreatitis.

PubMed: 36376282
DOI: 10.1038/s41467-022-34364-9

実験手法

ELECTRON MICROSCOPY (3.1 Å)