Molecular Organization and Assembly of the Export Apparatus of Flagellar Type III Secretion Systems

Minamino, Tetsuo; Kawamoto, Akihiro; Kinoshita, Miki; Namba, Keiichi

doi:10.1007/82_2019_170

Cited by 30 publications

(25 citation statements)

References 98 publications

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“…Secreted FlgM is further degraded extracellularly by the proteases Epr and WprA (Calvo and Kearns, 2015). It is currently well known that FliK plays an essential role in switching the substrate specificity of the flagellar export apparatus by modifying the export gate proteins FlhA and FlhB that control flagellar protein export (Aizawa, 2012;Hughes, 2012a,b;Evans et al, 2014;Minamino, 2018;Minamino et al, 2019;Kinoshita et al, 2020). This modification allows specificity switch for the secretion among others of filament class proteins (Ghelardi et al, 2002;Bouillaut et al, 2005;Minamino, 2018).…”

Section: Discussionmentioning

confidence: 99%

The fliK Gene Is Required for the Resistance of Bacillus thuringiensis to Antimicrobial Peptides and Virulence in Drosophila melanogaster

et al. 2020

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Antimicrobial peptides (AMPs) are essential effectors of the host innate immune system and they represent promising molecules for the treatment of multidrug resistant microbes. A better understanding of microbial resistance to these defense peptides is thus prerequisite for the control of infectious diseases. Here, using a random mutagenesis approach, we identify the fliK gene, encoding an internal molecular ruler that controls flagella hook length, as an essential element for Bacillus thuringiensis resistance to AMPs in Drosophila. Unlike its parental strain, that is highly virulent to both wild-type and AMPs deficient mutant flies, the fliK deletion mutant is only lethal to the latter’s. In agreement with its conserved function, the fliK mutant is non-flagellated and exhibits highly compromised motility. However, comparative analysis of the fliK mutant phenotype to that of a fla mutant, in which the genes encoding flagella proteins are interrupted, indicate that B. thuringiensis FliK-dependent resistance to AMPs is independent of flagella assembly. As a whole, our results identify FliK as an essential determinant for B. thuringiensis virulence in Drosophila and provide new insights on the mechanisms underlying bacteria resistance to AMPs.

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Section: Discussionmentioning

confidence: 99%

The fliK Gene Is Required for the Resistance of Bacillus thuringiensis to Antimicrobial Peptides and Virulence in Drosophila melanogaster

et al. 2020

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“…The sorting platform also functions as the recognition domain for effectors. It receives them from chaperone proteins and unfolds the effectors for secretion as folded proteins are too large to enter the needle (~2.5 nm inner diameter) [ 39 , 40 , 41 ]. Once the secreted proteins pass into the host cell, they elicit specific responses to reprogram the host’s machinery to enable colonization.…”

Section: Introductionmentioning

confidence: 99%

Molecular Targets and Strategies for Inhibition of the Bacterial Type III Secretion System (T3SS); Inhibitors Directly Binding to T3SS Components

2021

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The type III secretion system (T3SS) is a virulence apparatus used by many Gram-negative pathogenic bacteria to cause infections. Pathogens utilizing a T3SS are responsible for millions of infections yearly. Since many T3SS knockout strains are incapable of causing systemic infection, the T3SS has emerged as an attractive anti-virulence target for therapeutic design. The T3SS is a multiprotein molecular syringe that enables pathogens to inject effector proteins into host cells. These effectors modify host cell mechanisms in a variety of ways beneficial to the pathogen. Due to the T3SS’s complex nature, there are numerous ways in which it can be targeted. This review will be focused on the direct targeting of components of the T3SS, including the needle, translocon, basal body, sorting platform, and effector proteins. Inhibitors will be considered a direct inhibitor if they have a binding partner that is a T3SS component, regardless of the inhibitory effect being structural or functional.

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“…For construction of the flagella on the cell surface, the flagellar type III secretion system (fT3SS) transports flagellar building blocks from the cytoplasm to the distal end of the growing flagellar structure 2 . The fT3SS is divided into three structural parts: a transmembrane export gate complex made of FlhA, FlhB, FliP, FliQ, and FliR, a substrate-chaperone-docking platform composed of the cytoplasmic domains of FlhA and FlhB (FlhA C and FlhB C ), and a cytoplasmic ATPase ring complex consisting of FliH, FliI, and FliJ 3 . The FlhA C –FlhB C -docking platform provides binding sites for the cytoplasmic ATPase complex, flagellar export chaperones (FlgN, FliS, FliT), and export substrates to mediate hierarchical protein targeting and secretion 4 .…”

Section: Introductionmentioning

confidence: 99%

The FlhA linker mediates flagellar protein export switching during flagellar assembly

et al. 2021

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The flagellar protein export apparatus switches substrate specificity from hook-type to filament-type upon hook assembly completion, thereby initiating filament assembly at the hook tip. The C-terminal cytoplasmic domain of FlhA (FlhAC) serves as a docking platform for flagellar chaperones in complex with their cognate filament-type substrates. Interactions of the flexible linker of FlhA (FlhAL) with its nearest FlhAC subunit in the FlhAC ring is required for the substrate specificity switching. To address how FlhAL brings the order to flagellar assembly, we analyzed the flhA(E351A/W354A/D356A) ΔflgM mutant and found that this triple mutation in FlhAL increased the secretion level of hook protein by 5-fold, thereby increasing hook length. The crystal structure of FlhAC(E351A/D356A) showed that FlhAL bound to the chaperone-binding site of its neighboring subunit. We propose that the interaction of FlhAL with the chaperon-binding site of FlhAC suppresses filament-type protein export and facilitates hook-type protein export during hook assembly.

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Molecular Organization and Assembly of the Export Apparatus of Flagellar Type III Secretion Systems

Cited by 30 publications

References 98 publications

The fliK Gene Is Required for the Resistance of Bacillus thuringiensis to Antimicrobial Peptides and Virulence in Drosophila melanogaster

The fliK Gene Is Required for the Resistance of Bacillus thuringiensis to Antimicrobial Peptides and Virulence in Drosophila melanogaster

Molecular Targets and Strategies for Inhibition of the Bacterial Type III Secretion System (T3SS); Inhibitors Directly Binding to T3SS Components

The FlhA linker mediates flagellar protein export switching during flagellar assembly

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