Makes caterpillars floppy-like effector-containing MARTX toxins require host ADP-ribosylation factor (ARF) proteins for systemic pathogenicity

Youngjin Lee, Byoung Sik Kim, Sanghyeon Choi, Eun Young Lee, Shinhye Park, Jungwon Hwang, Yumi Kwon, Jaekyung Hyun, Cheolju Lee, Jihyun F. Kim, Soo Hyun Eom, Myung Hee Kima

Research output: Contribution to journalArticle

Abstract

Upon invading target cells, multifunctional autoprocessing repeatsin- toxin (MARTX) toxins secreted by bacterial pathogens release their disease-related modularly structured effector domains. However, it is unclear how a diverse repertoire of effector domains within these toxins are processed and activated. Here, we report that Makes caterpillars floppy-like effector (MCF)-containing MARTX toxins require ubiquitous ADP-ribosylation factor (ARF) proteins for processing and activation of intermediate effector modules, which localize in different subcellular compartments following limited processing of holo effector modules by the internal cysteine protease. Effector domains structured tandemly with MCF in intermediate modules become disengaged and fully activated by MCF, which aggressively interacts with ARF proteins present at the same location as intermediate modules and is converted allosterically into a catalytically competent protease. MCF-mediated effector processing leads ultimately to severe virulence in mice via an MCF-mediated ARF switching mechanism across subcellular compartments. This work provides insight into how bacteria take advantage of host systems to induce systemic pathogenicity.

Original languageEnglish
Pages (from-to)18031-18040
Number of pages10
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number36
DOIs
Publication statusPublished - 2019 Sep 3

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ADP-Ribosylation Factors
Virulence
Bacterial Toxins
Proteins
Cysteine Proteases
Peptide Hydrolases
Bacteria

All Science Journal Classification (ASJC) codes

  • General

Cite this

Lee, Youngjin ; Kim, Byoung Sik ; Choi, Sanghyeon ; Lee, Eun Young ; Park, Shinhye ; Hwang, Jungwon ; Kwon, Yumi ; Hyun, Jaekyung ; Lee, Cheolju ; Kim, Jihyun F. ; Eom, Soo Hyun ; Kima, Myung Hee. / Makes caterpillars floppy-like effector-containing MARTX toxins require host ADP-ribosylation factor (ARF) proteins for systemic pathogenicity. In: Proceedings of the National Academy of Sciences of the United States of America. 2019 ; Vol. 116, No. 36. pp. 18031-18040.
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Makes caterpillars floppy-like effector-containing MARTX toxins require host ADP-ribosylation factor (ARF) proteins for systemic pathogenicity. / Lee, Youngjin; Kim, Byoung Sik; Choi, Sanghyeon; Lee, Eun Young; Park, Shinhye; Hwang, Jungwon; Kwon, Yumi; Hyun, Jaekyung; Lee, Cheolju; Kim, Jihyun F.; Eom, Soo Hyun; Kima, Myung Hee.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 116, No. 36, 03.09.2019, p. 18031-18040.

Research output: Contribution to journalArticle

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