DataSheet2_A structural discovery journey of streptococcal phages adhesion devices by AlphaFold2.PDF

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异性识别和附着。侵袭革兰氏阳性细菌的拟噬菌体附着装置种类繁多，其中大部分仍处于理解不足的状态。这些组装体通常由长、柔韧和多结构域蛋白组成，这限制了通过如X射线晶体学、电子显微镜等实验方法对其结构分析。然而，AlphaFold2蛋白质结构预测程序却能精确地揭示此类分子机械的结构与功能细节。本研究中，我们展示了侵袭乳酸菌Streptococcus thermophilus的五个代表性拟噬菌体完整附着装置的结构预测结果。这些预测突显了这些装置的镶嵌性质，它们共享功能域，从而可以明确识别活性位点和残基。此类由AlphaFold2对噬菌体编码的宿主附着装置进行的分析，有望成为表征噬菌体-宿主相互作用机制的标准方法，并能够可靠地注释噬菌体基因组。