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Title: Structures of EccB1 and EccD1 from the core complex of the mycobacterial ESX-1 type VII secretion system

The ESX-1 type VII secretion system is an important determinant of virulence in pathogenic mycobacteria, including Mycobacterium tuberculosis. This complicated molecular machine secretes folded proteins through the mycobacterial cell envelope to subvert the host immune response. Despite its important role in disease very little is known about the molecular architecture of the ESX-1 secretion system. This study characterizes the structures of the soluble domains of two conserved core ESX-1 components – EccB1 and EccD1. The periplasmic domain of EccB1 consists of 4 repeat domains and a central domain, which together form a quasi 2-fold symmetrical structure. The repeat domains of EccB1 are structurally similar to a known peptidoglycan binding protein suggesting a role in anchoring the ESX-1 system within the periplasmic space. The cytoplasmic domain of EccD1 has a ubiquitin-like fold and forms a dimer with a negatively charged groove. In conclusion, these structures represent a major step towards resolving the molecular architecture of the entire ESX-1 assembly and may contribute to ESX-1 targeted tuberculosis intervention strategies.
Authors:
 [1] ;  [2] ;  [3] ;  [2] ;  [2] ;  [2] ;  [2] ;  [3]
  1. Univ. of Kentucky, Lexington, KY (United States); Univ. of Virginia, Charlottesville, VA (United States)
  2. Univ. of California, Los Angeles, CA (United States)
  3. Univ. of Kentucky, Lexington, KY (United States)
Publication Date:
OSTI Identifier:
1249240
Grant/Contract Number:
FC02-02ER63421; W-31-109-Eng-38.; 23616-002-06 F3:02; P30GM110787; P20GM103486
Type:
Accepted Manuscript
Journal Name:
BMC Structural Biology (Online)
Additional Journal Information:
Journal Name: BMC Structural Biology (Online); Journal Volume: 16; Journal Issue: 1; Journal ID: ISSN 1472-6807
Publisher:
BioMed Central
Research Org:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS); Univ. of Kentucky, Lexington, KY (United States)
Sponsoring Org:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22); US National Institutes of Health (NIH/NIGMS); USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; EccB; EccD; Mycobacterium tuberculosis; Type VII secretion system; ESX