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Structure of the M ycobacterium tuberculosis type VII secretion system chaperone EspG 5 in complex with PE 25– PPE 41 dimer
Author(s) -
Korotkova Natalia,
Freire Diana,
Phan Trang H.,
Ummels Roy,
Creekmore Christopher C.,
Evans Timothy J.,
Wilmanns Matthias,
Bitter Wilbert,
Parret Annabel H. A.,
Houben Edith N. G.,
Korotkov Konstantin V.
Publication year - 2014
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.12770
Subject(s) - secretion , chaperone (clinical) , biology , cytoplasm , secretory protein , microbiology and biotechnology , transport protein , effector , biogenesis , virulence , biochemistry , gene , medicine , pathology
Summary The growth or virulence of M ycobacterium 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 PE 25– PPE 41 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 PPE 41 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.