6PJU

Time-resolved structural snapshot of proteolysis by GlpG inside the membrane

6PJU の概要

• エントリーDOI: 10.2210/pdb6pju/pdb
• 分子名称: Rhomboid protease GlpG, Peptide aldehyde inhibitor (3 entities in total)
• 機能のキーワード: substrate complex, membrane protein, membrane protein-inhibitor complex, membrane protein/inhibitor
• 由来する生物種: Escherichia coli; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 25325.03

構造登録者

Urban, S.,Cho, S. (登録日: 2019-06-28, 公開日: 2019-11-27, 最終更新日: 2023-10-11)

主引用文献

Cho, S.,Baker, R.P.,Ji, M.,Urban, S.
Ten catalytic snapshots of rhomboid intramembrane proteolysis from gate opening to peptide release.
Nat.Struct.Mol.Biol., 26:910-918, 2019

PubMed Abstract: Protein cleavage inside the cell membrane triggers various pathophysiological signaling pathways, but the mechanism of catalysis is poorly understood. We solved ten structures of the Escherichia coli rhomboid protease in a bicelle membrane undergoing time-resolved steps that encompass the entire proteolytic reaction on a transmembrane substrate and an aldehyde inhibitor. Extensive gate opening accompanied substrate, but not inhibitor, binding, revealing that substrates and inhibitors take different paths to the active site. Catalysis unexpectedly commenced with, and was guided through subsequent catalytic steps by, motions of an extracellular loop, with local contributions from active site residues. We even captured the elusive tetrahedral intermediate that is uncleaved but covalently attached to the catalytic serine, about which the substrate was forced to bend dramatically. This unexpectedly stable intermediate indicates rhomboid catalysis uses an unprecedented reaction coordinate that may involve mechanically stressing the peptide bond, and could be selectively targeted by inhibitors.

PubMed: 31570873
DOI: 10.1038/s41594-019-0296-9

実験手法

X-RAY DIFFRACTION (2.5 Å)