Membrane insertion of α-xenorhabdolysin in near-atomic detail

ELife
Evelyn SchubertStefan Raunser

Abstract

α-Xenorhabdolysins (Xax) are α-pore-forming toxins (α-PFT) that form 1-1.3 MDa large pore complexes to perforate the host cell membrane. PFTs are used by a variety of bacterial pathogens to attack host cells. Due to the lack of structural information, the molecular mechanism of action of Xax toxins is poorly understood. Here, we report the cryo-EM structure of the XaxAB pore complex from Xenorhabdus nematophila and the crystal structures of the soluble monomers of XaxA and XaxB. The structures reveal that XaxA and XaxB are built similarly and appear as heterodimers in the 12-15 subunits containing pore, classifying XaxAB as bi-component α-PFT. Major conformational changes in XaxB, including the swinging out of an amphipathic helix are responsible for membrane insertion. XaxA acts as an activator and stabilizer for XaxB that forms the actual transmembrane pore. Based on our results, we propose a novel structural model for the mechanism of Xax intoxication.

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Citations

Aug 26, 2018·Toxins·Bastian Bräuning, Michael Groll
Mar 22, 2019·Proceedings of the National Academy of Sciences of the United States of America·Kaiming ZhangWah Chiu
Jan 17, 2021·Nature Communications·Uday TakMichael Niederweis
Feb 13, 2021·Toxins·Yajuan LiTengchuan Jin
Feb 22, 2021·Toxicon : Official Journal of the International Society on Toxinology·Amit AhujaVishal Singh Somvanshi
Mar 21, 2021·Scientific Reports·Alicia M Churchill-AngusPatrick J Baker
Nov 9, 2021·Biochemical Society Transactions·Joshua T Benton, Charles Bayly-Jones
Nov 21, 2021·Proceedings of the National Academy of Sciences of the United States of America·Aftab NadeemKarina Persson
Dec 1, 2021·Nature Communications·Minghao ChenChristos Gatsogiannis

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Methods Mentioned

BETA
X-ray
electron cryomicroscopy
size exclusion chromatography
electron microscopy
size
size-exclusion chromatography

Software Mentioned

PHYRE2
SHELX C / D
Beautifier
PARROT
MotionCor2
PostRefiner
phenix refine
MOLPROBITY
LocalFilter
RVIPER

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