Partial Atomic Model of the Tailed Lactococcal Phage TP901-1 as Predicted by AlphaFold2: Revelations and Limitations

Jennifer Mahony (1, 2, 3) , Adeline Goulet (4, 5, 6) , Douwe van Sinderen (1, 2, 3) , Christian Cambillau (1, 4)

1 UCC - University College Cork
2 School of Microbiology
3 APC Microbiome Institute [Cork]
4 LISM - Laboratoire d'ingénierie des systèmes macromoléculaires
5 CNRS - Centre National de la Recherche Scientifique
6 AMU - Aix Marseille Université

Bacteria are engaged in a constant battle against preying viruses, called bacteriophages (or phages). These remarkable nano-machines pack and store their genomes in a capsid and inject it into the cytoplasm of their bacterial prey following specific adhesion to the host cell surface. Tailed phages possessing dsDNA genomes are the most abundant phages in the bacterial virosphere, particularly those with long, non-contractile tails. All tailed phages possess a nano-device at their tail tip that specifically recognizes and adheres to a suitable host cell surface receptor, being proteinaceous and/or saccharidic. Adhesion devices of tailed phages infecting Gram-positive bacteria are highly diverse and, for the majority, remain poorly understood. Their long, flexible, multi-domain-encompassing tail limits experimental approaches to determine their complete structure. We have previously shown that the recently developed protein structure prediction program AlphaFold2 can overcome this limitation by predicting the structures of phage adhesion devices with confidence. Here, we extend this approach and employ AlphaFold2 to determine the structure of a complete phage, the lactococcal P335 phage TP901-1. Herein we report the structures of its capsid and neck, its extended tail, and the complete adhesion device, the baseplate, which was previously partially determined using X-ray crystallography.

Mots clés: bacteriophage; virion structure; Lactococcus; structural biology; AlphaFold2; P335; TP901-1

Domaines: Sciences du Vivant [q-bio]

Jennifer Mahony, Adeline Goulet, Douwe van Sinderen, Christian Cambillau. Partial Atomic Model of the Tailed Lactococcal Phage TP901-1 as Predicted by AlphaFold2: Revelations and Limitations. Viruses, 2023, 15, ⟨10.3390/v15122440⟩. ⟨hal-04448703⟩