Structure Report for: 6II2

Lee, Y., Kim, B.S., Choi, S., Lee, E.Y., Park, S., Hwang, J., Kwon, Y., Hyung, J., Lee, C., Eom, S.H., Kim, M.H.
Precursor of a multifunctional toxin that causes destruction of the actin
cytoskeleton by covalent cross-linking of actin and inactivation of Rho GTPases
when translocated into the host cytoplasm. Upon translocation into the host
cell, undergoes autoprocessing in cis mediated by the peptidase C80 domain
(also named CPD domain). One of the liberated protein is an alpha/beta hydrolase
which has a phosphatidylinositol-3-phosphate-specific phospholipase A1
activity which inhibits autophagy and endosomal trafficking

Title: Makes caterpillars floppy-like effector-containing MARTX toxins require host ADP-ribosylation factor (ARF) proteins for systemic pathogenicity
Lee Y, Kim BS, Choi S, Lee EY, Park S, Hwang J, Kwon Y, Hyun J, Lee C and Kim MH <2 more author(s)> Lee Y, Kim BS, Choi S, Lee EY, Park S, Hwang J, Kwon Y, Hyun J, Lee C, Kim JF, Eom SH, Kim MH (- 2)
Ref: Proc Natl Acad Sci U S A, 116:18031, 2019 : PubMed
Abstract


ESTHER: Lee_2019_Proc.Natl.Acad.Sci.U.S.A_116_18031
PubMedSearch: Lee 2019 Proc.Natl.Acad.Sci.U.S.A 116 18031
PubMedID: 31427506
Gene_locus related to this paper: vibvy-q7mdk6

Abstract

Upon invading target cells, multifunctional autoprocessing repeats-in-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.