Structure and activation mechanism of the Makes caterpillars floppy 1 toxin

Alexander Belyy1, Philipp Heilen1, Philine Hagel1

  • 1Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Otto-Hahn-Str. 11, 44227, Dortmund, Germany.

Nature Communications
|December 12, 2023
PubMed

Insights

The bacterial Makes caterpillars floppy 1 (Mcf1) toxin causes insect death by promoting apoptosis. Its unique activation mechanism involves host cell binding, leading to effector release and insect death.

Area of Science:

  • Molecular Biology
  • Structural Biology
  • Insect Pathology

Background:

  • The bacterial Makes caterpillars floppy 1 (Mcf1) toxin induces apoptosis in insects, causing significant mortality.
  • The precise molecular mechanisms governing Mcf1 intoxication remain largely unelucidated.

Purpose of the Study:

  • To determine the cryo-electron microscopy (cryo-EM) structure of the Mcf1 toxin.
  • To elucidate the molecular mechanism of Mcf1 activation and effector release.

Main Methods:

  • Cryo-electron microscopy (cryo-EM) to determine the structure of Mcf1.
  • Biochemical assays to analyze toxin activation and effector release.

Main Results:

  • The Mcf1 toxin possesses a seahorse-like structure with distinct head and tail domains.
  • Host cell binding to ADP-ribosylation factor 3 triggers conformational changes and autocleavage, releasing two toxic effectors.
  • The activator-binding domain (ABD) contains a BH3-like motif but is not an active effector.

Conclusions:

  • The study reveals a novel activation mechanism for the Mcf1 toxin involving host cell interaction and autocleavage.
  • Understanding Mcf1's structure and activation provides molecular insights into insecticidal toxin function and potential applications.

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