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Structure paper

TitleStructure and activation mechanism of the Makes caterpillars floppy 1 toxin.
Journal, issue, pagesNat Commun, Vol. 14, Issue 1, Page 8226, Year 2023
Publish dateDec 12, 2023
AuthorsAlexander Belyy / Philipp Heilen / Philine Hagel / Oliver Hofnagel / Stefan Raunser /
PubMed AbstractThe 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 linksNat Commun / PubMed:38086871 / PubMed Central
MethodsEM (single particle)
Resolution3.55 - 4.3 Å
Structure data

17435

8p50

EMDB-17435, PDB-8p50:
Photorhabdus luminescens Makes caterpillars floppy (Mcf) toxin with the C-terminal deletion in complex with Arf3
Method: EM (single particle) / Resolution: 4.04 Å

17436

8p51

EMDB-17436, PDB-8p51:
Photorhabdus luminescens Makes caterpillars floppy (Mcf) toxin with the C-terminal deletion
Method: EM (single particle) / Resolution: 3.55 Å

EMDB-17437: Photorhabdus luminescens Makes caterpillars floppy (Mcf) toxin, the central region of the toxin
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-17438: Photorhabdus luminescens Makes caterpillars floppy (Mcf) toxin, the tail region of the toxin
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-17439: Photorhabdus luminescens Makes caterpillars floppy (Mcf) toxin, the head of the toxin
Method: EM (single particle) / Resolution: 4.1 Å

17440

8p52

EMDB-17440, PDB-8p52:
Photorhabdus luminescens Makes caterpillars floppy (Mcf) toxin
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-17450: Photorhabdus luminescens Makes caterpillars floppy (Mcf) toxin, the low-resolution consensus map
Method: EM (single particle) / Resolution: 4.3 Å

Chemicals

ChemComp-GTP:
GUANOSINE-5'-TRIPHOSPHATE / GTP, energy-carrying molecule*YM / Guanosine triphosphate

ChemComp-MG:
Unknown entry

Source
  • photorhabdus luminescens (bacteria)
  • homo sapiens (human)
KeywordsTOXIN / Bacterial toxin / Arf

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