4KXR

Structure of the Mycobacterium tuberculosis type VII secretion system chaperone EspG5 in complex with PE25-PPE41 dimer

4KXR の概要

• エントリーDOI: 10.2210/pdb4kxr/pdb
• 分子名称: PE25, PPE41, EspG5, ... (4 entities in total)
• 機能のキーワード: esx-5, type vii secretion system, protein secretion, chaperone, protein transport
• 由来する生物種: Mycobacterium tuberculosis; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 65289.52

構造登録者

Korotkova, N.,Creekmore, C.C.,Korotkov, K.V. (登録日: 2013-05-27, 公開日: 2014-05-28, 最終更新日: 2023-09-20)

主引用文献

Korotkova, N.,Freire, D.,Phan, T.H.,Ummels, R.,Creekmore, C.C.,Evans, T.J.,Wilmanns, M.,Bitter, W.,Parret, A.H.,Houben, E.N.,Korotkov, K.V.
Structure of the Mycobacterium tuberculosis type VII secretion system chaperone EspG5 in complex with PE25-PPE41 dimer.
Mol.Microbiol., 94:367-382, 2014

PubMed Abstract: The growth or virulence of Mycobacterium tuberculosis bacilli depends on homologous type VII secretion systems, ESX-1, ESX-3 and ESX-5, which export a number of protein effectors across membranes to the bacterial surface and environment. PE and PPE proteins represent two large families of highly polymorphic proteins that are secreted by these ESX systems. Recently, it was shown that these proteins require system-specific cytoplasmic chaperones for secretion. Here, we report the crystal structure of M. tuberculosis ESX-5-secreted PE25-PPE41 heterodimer in complex with the cytoplasmic chaperone EspG(5). EspG(5) represents a novel fold that is unrelated to previously characterized secretion chaperones. Functional analysis of the EspG(5) -binding region uncovered a hydrophobic patch on PPE41 that promotes dimer aggregation, and the chaperone effectively abolishes this process. We show that PPE41 contains a characteristic chaperone-binding sequence, the hh motif, which is highly conserved among ESX-1-, ESX-3- and ESX-5-specific PPE proteins. Disrupting the interaction between EspG(5) and three different PPE target proteins by introducing different point mutations generally affected protein secretion. We further demonstrate that the EspG(5) chaperone plays an important role in the ESX secretion mechanism by keeping aggregation-prone PE-PPE proteins in their soluble state.

PubMed: 25155747
DOI: 10.1111/mmi.12770

実験手法

X-RAY DIFFRACTION (2.6 Å)