DataSheet1_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与粘附。侵袭革兰氏阳性菌的噬菌体粘附装置种类繁多，其中大部分仍处于理解不足的状态。这些装置通常由长、柔韧的多结构域蛋白组成，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的分析。然而，蛋白质结构预测程序AlphaFold2对于揭示此类分子机器的结构和功能细节具有极高的适应性。在本研究中，我们展示了五例代表性噬菌体感染嗜热链球菌（一种在乳品发酵中用作主要乳酸菌的菌株）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，它们共享具有明确活性位点和残基的功能域。此类基于AlphaFold2对噬菌体编码的宿主粘附装置的分析有望成为表征噬菌体-宿主相互作用机制和可靠注释噬菌体基因组的一种标准方法。