Structural highlights
4kxr is a 3 chain structure with sequence from Myctu. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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Gene: | Rv2431c, RVBD_2431c (MYCTU), RV2430c, RVBD_2430c (MYCTU), Rv1794, RVBD_1794 (MYCTU) |
Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Publication Abstract from PubMed
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 EspG5 . EspG5 represents a novel fold that is unrelated to previously characterized secretion chaperones. Functional analysis of the EspG5 -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 EspG5 and three different PPE target proteins by introducing different point mutations generally affected protein secretion. We further demonstrate that the EspG5 chaperone plays an important role in the ESX secretion mechanism by keeping aggregation-prone PE-PPE proteins in their soluble state.
Structure of the Mycobacterium tuberculosis type VII secretion system chaperone EspG in complex with PE25-PPE41 dimer.,Korotkova N, Freire D, Phan TH, Ummels R, Creekmore CC, Evans TJ, Wilmanns M, Bitter W, Parret AH, Houben EN, Korotkov KV Mol Microbiol. 2014 Aug 26. doi: 10.1111/mmi.12770. PMID:25155747[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Korotkova N, Freire D, Phan TH, Ummels R, Creekmore CC, Evans TJ, Wilmanns M, Bitter W, Parret AH, Houben EN, Korotkov KV. Structure of the Mycobacterium tuberculosis type VII secretion system chaperone EspG in complex with PE25-PPE41 dimer. Mol Microbiol. 2014 Aug 26. doi: 10.1111/mmi.12770. PMID:25155747 doi:http://dx.doi.org/10.1111/mmi.12770