6KYT

The structure of the M. tb toxin MazEF-mt1 complex


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.230 
  • R-Value Work: 0.195 
  • R-Value Observed: 0.196 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

Conserved Conformational Changes in the Regulation ofMycobacterium tuberculosisMazEF-mt1.

Chen, R.Zhou, J.Sun, R.Du, C.Xie, W.

(2020) ACS Infect Dis 6: 1783-1795

  • DOI: https://doi.org/10.1021/acsinfecdis.0c00048
  • Primary Citation of Related Structures:  
    6KYS, 6KYT, 6L29, 6L2A

  • PubMed Abstract: 

    Toxin-antitoxin (TA) systems, which regulate many important cellular processes, are abundantly present in prokaryotic organisms. MazEF is a common type of TA system implicated in the formation of "persisters cells" of the pathogen Mycobacterium tuberculosis , which contains 10 such systems. However, the exact function and inhibition mode of each MazF protein are not quite understood. Here, we report four high-resolution crystal structures of MazF-mt1 in various forms, including one in complex with MazE-mt1. The toxin displayed two unique interlocked loops that allow the formation of a tight dimer. These loops would open upon interacting with the MazE-mt1 antitoxin mediated by the last two helices of MazE-mt1. With our structure-based design, a mutant that could bind to the antitoxin with an enhanced affinity was produced. Combined crystallographic and biochemical studies further revealed that the binding affinity of MazE-mt1 to MazF-mt1 was mainly attributed to its α3 helical region, while the terminal helix η1 contributes very little or even negatively to the association of the pair, in stark contrast to the MazEF-mt9 system. This study provides structural insight into the binding mode and the inhibition mechanism of the MazE/F-mt1 TA pair, which may reflect the functional differences between different TA systems.


  • Organizational Affiliation

    MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory for Biocontrol, School of Life Sciences, The Sun Yat-Sen University, Guangzhou, Guangdong 510006, People's Republic of China.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Endoribonuclease MazF9122Mycobacterium tuberculosis H37RvMutation(s): 0 
Gene Names: mazF9mazF-mt1Rv2801c
EC: 3.1
UniProt
Find proteins for P71650 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
Explore P71650 
Go to UniProtKB:  P71650
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP71650
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Antitoxin MazE9C [auth P],
F,
K [auth Q],
L [auth C]
82Mycobacterium tuberculosis H37RvMutation(s): 0 
Gene Names: mazE9mazE-mt1Rv2801A
UniProt
Find proteins for P0CL61 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
Explore P0CL61 
Go to UniProtKB:  P0CL61
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP0CL61
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.230 
  • R-Value Work: 0.195 
  • R-Value Observed: 0.196 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 51.697α = 90
b = 161.14β = 99.628
c = 78.851γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
PHENIXrefinement
HKL-3000data reduction
HKL-3000data scaling
MOLREPphasing

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Natural Science Foundation of China (NSFC)China31870782

Revision History  (Full details and data files)

  • Version 1.0: 2020-08-05
    Type: Initial release
  • Version 1.1: 2023-11-22
    Changes: Data collection, Database references, Refinement description