The substrate specificity switch FlhB assembles onto the export gate to regulate type three secretion.

Nature Communications
Lucas KuhlenSusan M Lea

Abstract

Protein secretion through type-three secretion systems (T3SS) is critical for motility and virulence of many bacteria. Proteins are transported through an export gate containing three proteins (FliPQR in flagella, SctRST in virulence systems). A fourth essential T3SS protein (FlhB/SctU) functions to "switch" secretion substrate specificity once the growing hook/needle reach their determined length. Here, we present the cryo-electron microscopy structure of an export gate containing the switch protein from a Vibrio flagellar system at 3.2 Å resolution. The structure reveals that FlhB/SctU extends the helical export gate with its four predicted transmembrane helices wrapped around FliPQR/SctRST. The unusual topology of the FlhB/SctU helices creates a loop wrapped around the bottom of the closed export gate. Structure-informed mutagenesis suggests that this loop is critical in gating secretion and we propose that a series of conformational changes in the T3SS trigger opening of the gate through interactions between FlhB/SctU and FliPQR/SctRST.

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Citations

Nov 4, 2020·Biomolecules·Brittany L Carroll, Jun Liu
Nov 4, 2020·Molecular Microbiology·Trishant R UmrekarMorgan Beeby
Dec 10, 2020·Microorganisms·Waad BajunaidFrançois-Xavier Campbell-Valois
Dec 1, 2020·Molecular Microbiology·Bailey Milne-DaviesAndreas Diepold
Feb 13, 2021·Biomolecules·Manuel Halte, Marc Erhardt
Jan 5, 2021·Nihon saikingaku zasshi. Japanese journal of bacteriology·Tatsuro NishikinoMichio Homma
May 2, 2021·Nature Microbiology·Steven JohnsonSusan M Lea
Jun 3, 2021·Microorganisms·Miguel Díaz-GuerreroBertha González-Pedrajo
Jun 30, 2021·Nature Communications·Svenja HüsingThibaud T Renault
Jul 24, 2021·Trends in Biochemical Sciences·Haidai HuNicholas M I Taylor
Jul 11, 2021·Nature Communications·Akihiro KawamotoKeiichi Namba
Aug 30, 2021·Journal of Molecular Biology·Biao YuanAnastassios Economou

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Methods Mentioned

BETA
electrophoresis
targeted mutations
PCR
motility
size-exclusion chromatography

Software Mentioned

Simple
MolProbity
Coot
CTFFIND4
Phenix
RaptorX
MotionCor
Relion
Image

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