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PreprintCited by 22Escherichia coli research studiesBacterial Genetics and BiotechnologyBiochemical and Structural Characterization

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Assembly and architecture of the type III secretion sorting platform

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Soto, J. Eduardo, Galán, Jorge E., Lara-Tejero, María·2022·Proceedings of the National Academy of Sciences
DOI 10.1101/2022.09.23.509200PMC PMC9907115

Preprint — published as 10.1073/pnas.2218010119 · Paper page

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Abstract

SUMMARY: Type III secretion systems are bacterial nanomachines specialized in protein delivery into target eukaryotic cells. The structural and functional complexity of these machines demand highly coordinated mechanisms for their assembly and operation. The sorting platform is a critical component of type III secretion machines that ensures the timely engagement and secretion of proteins destined to travel this export pathway. However, the mechanisms that lead to the assembly of this multi-component structure have not been elucidated. Herein, employing structure modeling and an extensive in vivo crosslinking strategy, we provide a detailed inter-subunit-contact survey of the entire sorting platform complex. Using the identified crosslinks as signatures for pairwise inter-subunit interactions in combination with systematic genetic deletions, we mapped the assembly process of this unique bacterial structure. Insights generated by this study could serve as the bases for the development of anti-virulence strategies to combat several medically important bacterial pathogens.

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Metadata

Authors
Soto, J. E., Galán, J. E., & Lara-Tejero, M.
Affiliations
Yale University (US)
Corresponding author
Galán, Jorge E.
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
openRxiv
Published
2022-09-24
Volume
119
Issue
51
Pages
e2218010119-e2218010119
ISSN
0027-8424 (ISSN-L)
DOI
10.1101/2022.09.23.509200
PMC
PMC9907115
OpenAlex
W4311587853
Cited by
22
References
1
Citations by year
2026: 8 · 2025: 7 · 2024: 2 · 2023: 5
FWCI
2.20
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • National Institute of Allergy and Infectious Diseases (R37AI030492, AI030492, AI126158)
  • Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases (AI126158, AI030492)
Topics
  • Life Sciences › Immunology and Microbiology › Microbiology › Escherichia coli research studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Structural Characterization
Keywords
type III secretion system, protein secretion, protein complex formation, intersubunit interactions, in vivo cross-linking, gene deletion, anti-virulence strategies, pathogenic bacteria
MeSH terms
Type III Secretion Systems, Bacterial Proteins, Salmonella typhimurium, Protein Transport

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