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Structure and mechanism of the two-component α-helical pore-forming toxin YaxAB.


ABSTRACT: Pore-forming toxins (PFT) are virulence factors that transform from soluble to membrane-bound states. The Yersinia YaxAB system represents a family of binary α-PFTs with orthologues in human, insect, and plant pathogens, with unknown structures. YaxAB was shown to be cytotoxic and likely involved in pathogenesis, though the molecular basis for its two-component lytic mechanism remains elusive. Here, we present crystal structures of YaxA and YaxB, together with a cryo-electron microscopy map of the YaxAB complex. Our structures reveal a pore predominantly composed of decamers of YaxA-YaxB heterodimers. Both subunits bear membrane-active moieties, but only YaxA is capable of binding to membranes by itself. YaxB can subsequently be recruited to membrane-associated YaxA and induced to present its lytic transmembrane helices. Pore formation can progress by further oligomerization of YaxA-YaxB dimers. Our results allow for a comparison between pore assemblies belonging to the wider ClyA-like family of α-PFTs, highlighting diverse pore architectures.

SUBMITTER: Brauning B 

PROVIDER: S-EPMC5935710 | biostudies-other | 2018 May

REPOSITORIES: biostudies-other

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Structure and mechanism of the two-component α-helical pore-forming toxin YaxAB.

Bräuning Bastian B   Bertosin Eva E   Praetorius Florian F   Ihling Christian C   Schatt Alexandra A   Adler Agnes A   Richter Klaus K   Sinz Andrea A   Dietz Hendrik H   Groll Michael M  

Nature communications 20180504 1


Pore-forming toxins (PFT) are virulence factors that transform from soluble to membrane-bound states. The Yersinia YaxAB system represents a family of binary α-PFTs with orthologues in human, insect, and plant pathogens, with unknown structures. YaxAB was shown to be cytotoxic and likely involved in pathogenesis, though the molecular basis for its two-component lytic mechanism remains elusive. Here, we present crystal structures of YaxA and YaxB, together with a cryo-electron microscopy map of t  ...[more]

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