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Title | Structure and activation mechanism of the Makes caterpillars floppy 1 toxin. |
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Journal, issue, pages | Nat Commun, Vol. 14, Issue 1, Page 8226, Year 2023 |
Publish date | Dec 12, 2023 |
Authors | Alexander Belyy / Philipp Heilen / Philine Hagel / Oliver Hofnagel / Stefan Raunser / |
PubMed 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 ...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. |
External links | Nat Commun / PubMed:38086871 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.55 - 4.3 Å |
Structure data | EMDB-17435, PDB-8p50: EMDB-17436, PDB-8p51: EMDB-17437: Photorhabdus luminescens Makes caterpillars floppy (Mcf) toxin, the central region of the toxin EMDB-17438: Photorhabdus luminescens Makes caterpillars floppy (Mcf) toxin, the tail region of the toxin EMDB-17439: Photorhabdus luminescens Makes caterpillars floppy (Mcf) toxin, the head of the toxin EMDB-17440, PDB-8p52: EMDB-17450: Photorhabdus luminescens Makes caterpillars floppy (Mcf) toxin, the low-resolution consensus map |
Chemicals | ChemComp-GTP: ChemComp-MG: |
Source |
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Keywords | TOXIN / Bacterial toxin / Arf |