6SGZ

Structure of protomer 2 of the ESX-3 core complex


Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.90 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Architecture of the mycobacterial type VII secretion system.

Famelis, N.Rivera-Calzada, A.Degliesposti, G.Wingender, M.Mietrach, N.Skehel, J.M.Fernandez-Leiro, R.Bottcher, B.Schlosser, A.Llorca, O.Geibel, S.

(2019) Nature 576: 321-325

  • DOI: https://doi.org/10.1038/s41586-019-1633-1
  • Primary Citation of Related Structures:  
    6SGW, 6SGX, 6SGY, 6SGZ

  • PubMed Abstract: 

    Host infection by pathogenic mycobacteria, such as Mycobacterium tuberculosis, is facilitated by virulence factors that are secreted by type VII secretion systems 1 . A molecular understanding of the type VII secretion mechanism has been hampered owing to a lack of three-dimensional structures of the fully assembled secretion apparatus. Here we report the cryo-electron microscopy structure of a membrane-embedded core complex of the ESX-3/type VII secretion system from Mycobacterium smegmatis. The core of the ESX-3 secretion machine consists of four protein components-EccB3, EccC3, EccD3 and EccE3, in a 1:1:2:1 stoichiometry-which form two identical protomers. The EccC3 coupling protein comprises a flexible array of four ATPase domains, which are linked to the membrane through a stalk domain. The domain of unknown function (DUF) adjacent to the stalk is identified as an ATPase domain that is essential for secretion. EccB3 is predominantly periplasmatic, but a small segment crosses the membrane and contacts the stalk domain. This suggests that conformational changes in the stalk domain-triggered by substrate binding at the distal end of EccC3 and subsequent ATP hydrolysis in the DUF-could be coupled to substrate secretion to the periplasm. Our results reveal that the architecture of type VII secretion systems differs markedly from that of other known secretion machines 2 , and provide a structural understanding of these systems that will be useful for the design of antimicrobial strategies that target bacterial virulence.


  • Organizational Affiliation

    Institute for Molecular Infection Biology, Julius-Maximilians-University Würzburg, Würzburg, Germany.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
ESX-3 secretion system protein EccD3A [auth E],
B [auth H]
467Mycolicibacterium smegmatis MC2 155Mutation(s): 0 
Gene Names: eccD3snmMSMEG_0623MSMEI_0607
Membrane Entity: Yes 
UniProt
Find proteins for A0QQ46 (Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155))
Explore A0QQ46 
Go to UniProtKB:  A0QQ46
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupA0QQ46
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
ESX-3 secretion system ATPase EccB3C [auth I]59Mycolicibacterium smegmatis MC2 155Mutation(s): 0 
Gene Names: eccB3MSMEG_0616MSMEI_0600
EC: 3.6
Membrane Entity: Yes 
UniProt
Find proteins for A0QQ39 (Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155))
Explore A0QQ39 
Go to UniProtKB:  A0QQ39
Entity Groups  
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UniProt GroupA0QQ39
Sequence Annotations
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
ESX-3 secretion system protein EccC3D [auth J]343Mycolicibacterium smegmatis MC2 155Mutation(s): 0 
Gene Names: eccC3MSMEG_0617MSMEI_0601
Entity Groups  
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  • Reference Sequence
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
ESX-3 secretion system protein EccE3E [auth D]286Mycolicibacterium smegmatis MC2 155Mutation(s): 0 
Gene Names: eccE3MSMEG_0626MSMEI_0609
Membrane Entity: Yes 
UniProt
Find proteins for A0QQ48 (Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155))
Explore A0QQ48 
Go to UniProtKB:  A0QQ48
Entity Groups  
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UniProt GroupA0QQ48
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.90 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 
EM Software:
TaskSoftware PackageVersion
MODEL REFINEMENTPHENIX1.15.2-3472
RECONSTRUCTIONRELION

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Spanish Ministry of Science, Innovation, and UniversitiesSpainSAF2017-82632-P o-funded by the European Regional Development Fund
European Regional Development FundSpainY2018/BIO4747 co-funded by the Autonomous Region of Madrid
European Regional Development FundSpainP2018/NMT4443 co-funded by Autonomous Region of Madrid
European UnionSpainHorizon 2020, iNEXT (PID2907) , Grant number 653706
Bavarian State Ministry of Science and the Arts Funding OrganisationGermanyN-BM-2013-246

Revision History  (Full details and data files)

  • Version 1.0: 2019-10-09
    Type: Initial release
  • Version 1.1: 2019-10-23
    Changes: Data collection, Database references
  • Version 1.2: 2019-12-25
    Changes: Database references
  • Version 1.3: 2024-05-22
    Changes: Data collection, Database references