Goulet Adeline, Joos Raphaela, Lavelle Katherine, Van Sinderen Douwe, Mahony Jennifer, Cambillau Christian
Laboratoire d'Ingénierie des Systèmes Macromoléculaires (LISM), Institut de Microbiologie, Bioénergies et Biotechnologie, CNRS, Aix-Marseille Université, UMR7255, Marseille, France.
School of Microbiology, University College Cork, Cork, Ireland.
Front Mol Biosci. 2022 Aug 19;9:960325. doi: 10.3389/fmolb.2022.960325. eCollection 2022.
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 , 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黏附。感染革兰氏阳性菌的肌尾噬菌体的黏附装置非常多样，而且在大多数情况下仍未被充分了解。这些组件通常由长的、灵活的多结构域蛋白质组成，这限制了通过X射线晶体学和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非常适合揭示此类分子机制的结构和功能细节。在这里，我们展示了五种感染嗜热栖热放线菌（一种用于乳制品发酵的主要乳酸菌）的代表性肌尾噬菌体完整黏附装置的结构预测。这些预测突出了这些装置的镶嵌性质，它们共享可以明确识别活性位点和残基的功能域。这种对噬菌体编码的宿主黏附装置的AlphaFold2分析应该成为表征噬菌体-宿主相互作用机制和可靠注释噬菌体基因组的标准方法。
