DataSheet3_A structural discovery journey of streptococcal phages adhesion devices by AlphaFold2.ZIP

Successful bacteriophage infection starts with specific recognition and adhesion to the 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 limits their structural analyses by experimental approaches such as X-ray crystallography and electron microscopy. However, 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 whole adhesion devices of five representative siphophages infecting Streptococcus thermophilus, one of the main lactic acid bacteria used in dairy fermentations. The predictions highlight the mosaic nature of these devices that share functional domains for which active sites and residues could be unambiguously identified. Such AlphaFold2 analyses of phage-encoded host adhesion devices should become a standard method to characterize phage-host interaction machineries and to reliably annotate phage genomes.

成功的噬菌体感染始于对宿主细胞表面的特定识别和粘附。侵袭革兰氏阳性细菌的拟噬菌体的粘附装置种类繁多，其中大部分仍处于理解不足的状态。这些组装通常由长、柔韧且多结构域的蛋白质组成，这限制了通过X射线晶体学、电子显微镜等实验方法对其进行结构分析。然而，蛋白质结构预测程序AlphaFold2却能够精确地揭示此类分子机器的结构和功能细节。在此，我们展示了五种代表性拟噬菌体感染嗜热链球菌（一种主要应用于乳制品发酵的乳酸菌）的整个粘附装置的结构预测。这些预测突显了这些装置的镶嵌特性，它们共享功能域，其活性位点与残基能够被明确识别。此类AlphaFold2对噬菌体编码的宿主粘附装置的分析应成为表征噬菌体-宿主相互作用机制和可靠注释噬菌体基因组的标准方法。