4QLP

Atomic structure of tuberculosis necrotizing toxin (TNT) complexed with its immunity factor IFT


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.10 Å
  • R-Value Free: 0.143 
  • R-Value Work: 0.129 
  • R-Value Observed: 0.129 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

The tuberculosis necrotizing toxin kills macrophages by hydrolyzing NAD.

Sun, J.Siroy, A.Lokareddy, R.K.Speer, A.Doornbos, K.S.Cingolani, G.Niederweis, M.

(2015) Nat Struct Mol Biol 22: 672-678

  • DOI: https://doi.org/10.1038/nsmb.3064
  • Primary Citation of Related Structures:  
    4QLP

  • PubMed Abstract: 

    Mycobacterium tuberculosis (Mtb) induces necrosis of infected cells to evade immune responses. Recently, we found that Mtb uses the protein CpnT to kill human macrophages by secreting its C-terminal domain, named tuberculosis necrotizing toxin (TNT), which induces necrosis by an unknown mechanism. Here we show that TNT gains access to the cytosol of Mtb-infected macrophages, where it hydrolyzes the essential coenzyme NAD(+). Expression or injection of a noncatalytic TNT mutant showed no cytotoxicity in macrophages or in zebrafish zygotes, respectively, thus demonstrating that the NAD(+) glycohydrolase activity is required for TNT-induced cell death. To prevent self-poisoning, Mtb produces an immunity factor for TNT (IFT) that binds TNT and inhibits its activity. The crystal structure of the TNT-IFT complex revealed a new NAD(+) glycohydrolase fold of TNT, the founding member of a toxin family widespread in pathogenic microorganisms.


  • Organizational Affiliation

    Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
immunity factor IFT176Mycobacterium tuberculosis H37RvMutation(s): 0 
Gene Names: HKBT1_4117Rv3902cRv3903cRVBD_3902cRVBD_3903c
UniProt
Find proteins for O05443 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
Explore O05443 
Go to UniProtKB:  O05443
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO05443
Sequence Annotations
Expand
  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Alanine and proline rich protein, tuberculosis necrotizing toxin (TNT)199Mycobacterium tuberculosis H37RvMutation(s): 0 
Gene Names: HKBT1_4118Rv3902cRv3903cRVBD_3902cRVBD_3903c
UniProt
Find proteins for O05442 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
Explore O05442 
Go to UniProtKB:  O05442
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO05442
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.10 Å
  • R-Value Free: 0.143 
  • R-Value Work: 0.129 
  • R-Value Observed: 0.129 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 70.618α = 90
b = 86.295β = 90
c = 62.691γ = 90
Software Package:
Software NamePurpose
ADSCdata collection
PHASERphasing
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2015-07-22
    Type: Initial release
  • Version 1.1: 2015-08-12
    Changes: Structure summary
  • Version 1.2: 2015-09-30
    Changes: Database references
  • Version 1.3: 2023-09-20
    Changes: Data collection, Database references, Refinement description