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bioRxiv · 10.1101/590430

Structure of a Tc holotoxin pore provides insights into the translocation mechanism

Roderer, D.·Hofnagel, O.·Benz, R.·Raunser, S.
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Abstract

Tc toxins are modular toxin systems that are composed of a pentameric membrane translocator (TcA) and a cocoon (TcB and TcC) encapsulating the toxic enzyme. Binding of Tcs to target cells and a pH shift trigger the conformational transition from the soluble prepore state to the membrane-embedded pore. Subsequently, the toxic enzyme is translocated and released into the cytoplasm. Here, we show in atomic detail an assembled Tc toxin complex from P. luminescens in the membrane. We find that the five TcA protomers conformationally adapt to fit around the cocoon during prepore-to-pore transition. The architecture of the Tc toxin complex also allows TcB-TcC to bind to an already membrane-embedded TcA pore to form a holotoxin. Mammalian lipids with zwitterionic head groups are preferred over other lipids for Tc toxin integration. The translocated toxic enzyme, which can be partially visualized, transiently interacts with alternating negative charges and hydrophobic stretches.

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Roderer, D., Hofnagel, O., Benz, R., Raunser, S.. 2019-03-26. Structure of a Tc holotoxin pore provides insights into the translocation mechanism. https://doi.org/10.1101/590430

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