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 journalArticlepeer-review

3 Citations (Scopus)

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

Bibliographical note

Funding Information:
ACKNOWLEDGMENTS. We thank beamline staff at the Pohang Accelerator Laboratory (BL-5C and 7A), Korea, and the Photon Factory (BL-17A), Japan, for assistance during X-ray diffraction experiments. We thank all members of the M.H.K. laboratory for valuable discussion and technical support. This work was supported by the National Research Foundation of Korea, funded by the Ministry of Science and ICT of Korea (2014R1A2A1A01005971 and 2017R1A2B3007317 to M.H.K. and 2018R1C1B5045632 to B.S.K.), the Korea Research Institute of Bioscience and Biotechnology Initiative Program, and a grant from Korea Health Industry Development Institute (HI14C3484 to C.L.).

All Science Journal Classification (ASJC) codes

  • General

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