3M91

Crystal structure of the prokaryotic ubiquitin-like protein (Pup) complexed with the amino terminal coiled coil of the Mycobacterium tuberculosis proteasomal ATPase Mpa

3M91 の概要

• エントリーDOI: 10.2210/pdb3m91/pdb
• 分子名称: Proteasome-associated ATPase, Prokaryotic ubiquitin-like protein pup (3 entities in total)
• 機能のキーワード: coil coil alpha helix, atp-binding, chaperone, nucleotide-binding, proteasome, s-nitrosylation, virulence, isopeptide bond, ubl conjugation pathway, hydrolase regulator
• 由来する生物種: Mycobacterium tuberculosis; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 21649.72

構造登録者

Wang, T.,Li, H. (登録日: 2010-03-19, 公開日: 2010-10-27, 最終更新日: 2024-02-21)

主引用文献

Wang, T.,Darwin, K.H.,Li, H.
Binding-induced folding of prokaryotic ubiquitin-like protein on the Mycobacterium proteasomal ATPase targets substrates for degradation.
Nat.Struct.Mol.Biol., 17:1352-1357, 2010

PubMed Abstract: Mycobacterium tuberculosis uses a proteasome system that is analogous to the eukaryotic ubiquitin-proteasome pathway and is required for pathogenesis. However, the bacterial analog of ubiquitin, prokaryotic ubiquitin-like protein (Pup), is an intrinsically disordered protein that bears little sequence or structural resemblance to the highly structured ubiquitin. Thus, it was unknown how pupylated proteins were recruited to the proteasome. Here, we show that the Mycobacterium proteasomal ATPase (Mpa) has three pairs of tentacle-like coiled coils that recognize Pup. Mpa bound unstructured Pup through hydrophobic interactions and a network of hydrogen bonds, leading to the formation of an α-helix in Pup. Our work describes a binding-induced folding recognition mechanism in the Pup-proteasome system that differs mechanistically from substrate recognition in the ubiquitin-proteasome system. This key difference between the prokaryotic and eukaryotic systems could be exploited for the development of a small molecule-based treatment for tuberculosis.

PubMed: 20953180
DOI: 10.1038/nsmb.1918

実験手法

X-RAY DIFFRACTION (1.8 Å)