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- Title
Structure and activation mechanism of the Makes caterpillars floppy 1 toxin.
- Authors
Belyy, Alexander; Heilen, Philipp; Hagel, Philine; Hofnagel, Oliver; Raunser, Stefan
- Abstract
The bacterial Makes caterpillars floppy 1 (Mcf1) toxin promotes apoptosis in insects, leading to loss of body turgor and death. The molecular mechanism underlying Mcf1 intoxication is poorly understood. Here, we present the cryo-EM structure of Mcf1 from Photorhabdus luminescens, revealing a seahorse-like shape with a head and tail. While the three head domains contain two effectors, as well as an activator-binding domain (ABD) and an autoprotease, the tail consists of two putative translocation and three putative receptor-binding domains. Rearrangement of the tail moves the C-terminus away from the ABD and allows binding of the host cell ADP-ribosylation factor 3, inducing conformational changes that position the cleavage site closer to the protease. This distinct activation mechanism that is based on a hook-loop interaction results in three autocleavage reactions and the release of two toxic effectors. Unexpectedly, the BH3-like domain containing ABD is not an active effector. Our findings allow us to understand key steps of Mcf1 intoxication at the molecular level. The bacterial toxin Makes caterpillars floppy 1 promotes apoptosis in insects. Combining single-particle cryo-EM and biochemistry, the authors determined the molecular architecture of the toxin and revealed its autoproteolytic activation mechanism.
- Subjects
CATERPILLARS; PHOTORHABDUS luminescens; TOXINS; ADP-ribosylation; BACTERIAL toxins; BIOCHEMISTRY; TURGOR
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-44069-2