Unconventional structure and mechanisms for membrane interaction and translocation of the NF-¿B-targeting toxin AIP56

• Type: Article in International Scientific Journal
• Date: 2023

Authors

Lisboa, J (Author) Other; Pereira, C (Author) Other; Pinto, D (Author) Other; Rodrigues, S (Author) Other; Pereira, MG (Author) Other; Pinheiro, B (Author) Other; oliveira, p (Author) ICBAS; Pereira, PJB (Author) Other; Azevedo, E (Author) Other; Durand, D (Author) Other; Benz, R (Author) Other; do Vale, A (Author) Other; dos Santos, MS (Author) Other

Journal

Title: Nature Communications

Vol. 14

ISSN: 2041-1723

Publisher: Springer Nature

Indexing

Scopus - 0 Citations

Other information

Authenticus ID: P-00Z-D5R

DOI: 10.1038/s41467-023-43054-z

Abstract (EN): 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. © 2023, The Author(s).

Language: English

Type (Professor's evaluation): Scientific