8SFG

Crystal Structure of the Open Unbound Catalytically Inactive Makes Caterpillars Floppy-like (MCF) Effector from Vibrio vulnificus CMCP6

Summary for 8SFG

• Entry DOI: 10.2210/pdb8sfg/pdb
• Descriptor: Autotransporter adhesin, SULFATE ION, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: center for structural biology of infectious diseases (csbid), structural genomics, center for structural genomics of infectious diseases, csgid, mcf, toxin
• Biological source: Vibrio vulnificus CMCP6
• Total number of polymer chains: 4
• Total formula weight: 163164.49

Authors

Minasov, G.,Shuvalova, L.,Rosas-Lemus, M.,Herrera, A.,Satchell, K.J.F.,Center for Structural Biology of Infectious Diseases (CSBID) (deposition date: 2023-04-11, release date: 2024-06-05, Last modification date: 2025-09-24)

Primary citation

Herrera, A.,Packer, M.M.,Rosas-Lemus, M.,Minasov, G.,Chen, J.,Brumell, J.H.,Satchell, K.J.F.
Vibrio MARTX toxin processing and degradation of cellular Rab GTPases by the cytotoxic effector Makes Caterpillars Floppy.
Proc.Natl.Acad.Sci.USA, 121:e2316143121-e2316143121, 2024

PubMed Abstract: causes life-threatening wound and gastrointestinal infections, mediated primarily by the production of a Multifunctional-Autoprocessing Repeats-In-Toxin (MARTX) toxin. The most commonly present MARTX effector domain, the Makes Caterpillars Floppy-like (MCF) toxin, is a cysteine protease stimulated by host adenosine diphosphate (ADP) ribosylation factors (ARFs) to autoprocess. Here, we show processed MCF then binds and cleaves host s-related proteins in rain (Rab) guanosine triphosphatases within their C-terminal tails resulting in Rab degradation. We demonstrate MCF binds Rabs at the same interface occupied by ARFs. Moreover, we show MCF preferentially binds to ARF1 prior to autoprocessing and is active to cleave Rabs only subsequent to autoprocessing. We then use structure prediction algorithms to demonstrate that structural composition, rather than sequence, determines Rab target specificity. We further determine a crystal structure of aMCF as a swapped dimer, revealing an alternative conformation we suggest represents the open, activated state of MCF with reorganized active site residues. The cleavage of Rabs results in Rab1B dispersal within cells and loss of Rab1B density in the intestinal tissue of infected mice. Collectively, our work describes an extracellular bacterial mechanism whereby MCF is activated by ARFs and subsequently induces the degradation of another small host guanosine triphosphatase (GTPase), Rabs, to drive organelle damage, cell death, and promote pathogenesis of these rapidly fatal infections.

PubMed: 38861595
DOI: 10.1073/pnas.2316143121

Experimental method

X-RAY DIFFRACTION (2.8 Å)