Exploring Structural Diversity among Adhesion Devices Encoded by Lactococcal P335 Phages with AlphaFold2.

Bacteriophages, or phages, are the most abundant biological entities on Earth. They possess molecular nanodevices to package and store their genome, as well as to introduce it into the cytoplasm of their bacterial prey. Successful phage infection commences with specific recognition of, and adhesion to, a suitable host cell surface. Adhesion devices of siphophages infecting Gram-positive bacteria are very diverse and remain, for the majority, poorly understood. These assemblies often comprise long, flexible, and multi-domain proteins, which limit their structural analyses by experimental approaches. The protein structure prediction program AlphaFold2 is exquisitely adapted to unveil structural and functional details of such molecular machineries. Here, we present structure predictions of adhesion devices from siphophages belonging to the P335 group infecting spp., one of the most extensively applied lactic acid bacteria in dairy fermentations. The predictions of representative adhesion devices from types I-IV P335 phages illustrate their very diverse topology. Adhesion devices from types III and IV phages share a common topology with that of p2, with a receptor binding protein anchored to the virion by a distal tail protein loop. This suggests that they exhibit an activation mechanism similar to that of phage p2 prior to host binding.