4KXR

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


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.244 
  • R-Value Work: 0.194 
  • R-Value Observed: 0.196 

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This is version 1.4 of the entry. See complete history


Literature

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

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.

(2014) Mol Microbiol 94: 367-382

  • DOI: https://doi.org/10.1111/mmi.12770
  • Primary Citation of Related Structures:  
    4KXR

  • 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.


  • Organizational Affiliation

    Department of Molecular & Cellular Biochemistry, University of Kentucky, Lexington, KY, 40536, USA; Center for Structural Biology, University of Kentucky, Lexington, KY, 40536, USA.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
PE25101Mycobacterium tuberculosis H37RvMutation(s): 0 
Gene Names: Rv2431cRVBD_2431c
UniProt
Find proteins for I6X486 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
Explore I6X486 
Go to UniProtKB:  I6X486
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupI6X486
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
PPE41194Mycobacterium tuberculosis H37RvMutation(s): 0 
Gene Names: RV2430cRVBD_2430c
UniProt
Find proteins for Q79FE1 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
Explore Q79FE1 
Go to UniProtKB:  Q79FE1
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ79FE1
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
EspG5300Mycobacterium tuberculosis H37RvMutation(s): 0 
Gene Names: Rv1794RVBD_1794
UniProt
Find proteins for O53943 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
Explore O53943 
Go to UniProtKB:  O53943
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO53943
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.244 
  • R-Value Work: 0.194 
  • R-Value Observed: 0.196 
  • Space Group: P 61 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 139.1α = 90
b = 139.1β = 90
c = 171.01γ = 120
Software Package:
Software NamePurpose
XSCALEdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction
SERGUIdata collection
XDSdata reduction
PHASERphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2014-05-28
    Type: Initial release
  • Version 1.1: 2014-08-27
    Changes: Database references
  • Version 1.2: 2014-09-03
    Changes: Database references
  • Version 1.3: 2014-10-22
    Changes: Database references
  • Version 1.4: 2023-09-20
    Changes: Data collection, Database references, Refinement description