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Structure paper

TitleTc toxin activation requires unfolding and refolding of a β-propeller.
Journal, issue, pagesNature, Vol. 563, Issue 7730, Page 209-213, Year 2018
Publish dateSep 19, 2018
AuthorsChristos Gatsogiannis / Felipe Merino / Daniel Roderer / David Balchin / Evelyn Schubert / Anne Kuhlee / Manajit Hayer-Hartl / Stefan Raunser /
PubMed AbstractTc toxins secrete toxic enzymes into host cells using a unique syringe-like injection mechanism. They are composed of three subunits, TcA, TcB and TcC. TcA forms the translocation channel and the TcB- ...Tc toxins secrete toxic enzymes into host cells using a unique syringe-like injection mechanism. They are composed of three subunits, TcA, TcB and TcC. TcA forms the translocation channel and the TcB-TcC heterodimer functions as a cocoon that shields the toxic enzyme. Binding of the cocoon to the channel triggers opening of the cocoon and translocation of the toxic enzyme into the channel. Here we show in atomic detail how the assembly of the three components activates the toxin. We find that part of the cocoon completely unfolds and refolds into an alternative conformation upon binding. The presence of the toxic enzyme inside the cocoon is essential for its subnanomolar binding affinity for the TcA subunit. The enzyme passes through a narrow negatively charged constriction site inside the cocoon, probably acting as an extruder that releases the unfolded protein with its C terminus first into the translocation channel.
External linksNature / PubMed:30232455
MethodsEM (single particle) / X-ray diffraction
Resolution3.004 - 3.95 Å
Structure data

0149

6h6e

EMDB-0149, PDB-6h6e:
PTC3 holotoxin complex from Photorhabdus luminecens in prepore state (TcdA1, TcdB2, TccC3)
Method: EM (single particle) / Resolution: 3.95 Å

0150

6h6f

EMDB-0150, PDB-6h6f:
PTC3 holotoxin complex from Photorhabdus luminiscens - Mutant TcC-D651A
Method: EM (single particle) / Resolution: 3.72 Å

PDB-6h6g:
Crystal Structure of TcdB2-TccC3 without hypervariable C-terminal region
Method: X-RAY DIFFRACTION / Resolution: 3.004 Å

Chemicals

ChemComp-HOH:
WATER / Water

Source
  • photorhabdus luminescens (bacteria)
KeywordsTOXIN / pore forming toxin / translocation / bacterial toxin / a-PFT / Photorhabdus / ABC / Tc / membrane transport / Tc toxin / ABC toxin

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