8FZ6

The human PI31 complexed with bovine 20S proteasome

8FZ6 の概要

• エントリーDOI: 10.2210/pdb8fz6/pdb
• 関連するPDBエントリー: 8FZ5
• EMDBエントリー: 29604
• 分子名称: Proteasome subunit alpha type-6, Proteasome subunit beta type-3, Proteasome subunit beta type-2, ... (15 entities in total)
• 機能のキーワード: pi31, inhibitor, 20s, proteasome, hydrolase
• 由来する生物種: Bos taurus (cattle); 詳細
• タンパク質・核酸の鎖数: 30
• 化学式量合計: 821356.57

構造登録者

Hsu, H.-C.,Li, H. (登録日: 2023-01-27, 公開日: 2023-07-05, 最終更新日: 2024-06-19)

主引用文献

Hsu, H.C.,Wang, J.,Kjellgren, A.,Li, H.,DeMartino, G.N.
Eta igh-resolution structure of mammalian PI31-20S proteasome complex reveals mechanism of proteasome inhibition.
J.Biol.Chem., 299:104862-104862, 2023

PubMed Abstract: Proteasome-catalyzed protein degradation mediates and regulates critical aspects of many cellular functions and is an important element of proteostasis in health and disease. Proteasome function is determined in part by the types of proteasome holoenzymes formed between the 20S core particle that catalyzes peptide bond hydrolysis and any of multiple regulatory proteins to which it binds. One of these regulators, PI31, was previously identified as an in vitro 20S proteasome inhibitor, but neither the molecular mechanism nor the possible physiologic significance of PI31-mediated proteasome inhibition has been clear. Here we report a high-resolution cryo-EM structure of the mammalian 20S proteasome in complex with PI31. The structure shows that two copies of the intrinsically disordered carboxyl terminus of PI31 are present in the central cavity of the closed-gate conformation of the proteasome and interact with proteasome catalytic sites in a manner that blocks proteolysis of substrates but resists their own degradation. The two inhibitory polypeptide chains appear to originate from PI31 monomers that enter the catalytic chamber from opposite ends of the 20S cylinder. We present evidence that PI31 can inhibit proteasome activity in mammalian cells and may serve regulatory functions for the control of cellular proteostasis.

PubMed: 37236357
DOI: 10.1016/j.jbc.2023.104862

実験手法

ELECTRON MICROSCOPY (2.54 Å)