7ZPF

Three-dimensional structure of AIP56, a short-trip single chain AB toxin from Photobacterium damselae subsp. piscicida.

Summary for 7ZPF

• Entry DOI: 10.2210/pdb7zpf/pdb
• Descriptor: Aip56, ZINC ION, NICKEL (II) ION, ... (5 entities in total)
• Functional Keywords: apoptosis-inducing protein of 56 kda, ab-toxin, zinc-metalloprotease, nf-kb p65 target, toxin
• Biological source: Photobacterium damselae subsp. piscicida (causative agent of fish pasteurellosis)
• Total number of polymer chains: 4
• Total formula weight: 237004.64

Authors

Lisboa, J.,Pereira, P.J.B.,dos Santos, N.M.S. (deposition date: 2022-04-27, release date: 2023-05-10, Last modification date: 2024-11-13)

Primary citation

Lisboa, J.,Pereira, C.,Pinto, R.D.,Rodrigues, I.S.,Pereira, L.M.G.,Pinheiro, B.,Oliveira, P.,Pereira, P.J.B.,Azevedo, J.E.,Durand, D.,Benz, R.,do Vale, A.,Dos Santos, N.M.S.
Unconventional structure and mechanisms for membrane interaction and translocation of the NF-kappa B-targeting toxin AIP56.
Nat Commun, 14:7431-7431, 2023

PubMed Abstract: Bacterial AB toxins are secreted key virulence factors that are internalized by target cells through receptor-mediated endocytosis, translocating their enzymatic domain to the cytosol from endosomes (short-trip) or the endoplasmic reticulum (long-trip). To accomplish this, bacterial AB toxins evolved a multidomain structure organized into either a single polypeptide chain or non-covalently associated polypeptide chains. The prototypical short-trip single-chain toxin is characterized by a receptor-binding domain that confers cellular specificity and a translocation domain responsible for pore formation whereby the catalytic domain translocates to the cytosol in an endosomal acidification-dependent way. In this work, the determination of the three-dimensional structure of AIP56 shows that, instead of a two-domain organization suggested by previous studies, AIP56 has three-domains: a non-LEE encoded effector C (NleC)-like catalytic domain associated with a small middle domain that contains the linker-peptide, followed by the receptor-binding domain. In contrast to prototypical single-chain AB toxins, AIP56 does not comprise a typical structurally complex translocation domain; instead, the elements involved in translocation are scattered across its domains. Thus, the catalytic domain contains a helical hairpin that serves as a molecular switch for triggering the conformational changes necessary for membrane insertion only upon endosomal acidification, whereas the middle and receptor-binding domains are required for pore formation.

PubMed: 37973928
DOI: 10.1038/s41467-023-43054-z

Experimental method

X-RAY DIFFRACTION (2.54 Å)