Deciphering Bacteriophage T5 Host Recognition Mechanism and Infection Trigger
Deciphering Bacteriophage T5 Host Recognition Mechanism and Infection Trigger
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DOI：
10.1128/jvi.01584-22
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发表时间：
2023-02-13
影响因子：
5.4
通讯作者：
Breyton, Cecile
中科院分区：
文献类型：
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作者：
Degroux, Seraphine;Effantin, Gregory;Breyton, Cecile
有尾噬菌体通过其受体结合蛋白（RBP）与位于其猎物表面的噬菌体和/或蛋白质的相互作用来特异性地识别其细菌宿主。这种关键的相互作用使病毒感染，但这种机制的分子细节对于大多数噬菌体来说是未知的。噬菌体，感染细菌的病毒，以高度特异性识别其宿主，结合到其宿主细胞壁的糖基序或蛋白质上。在大多数噬菌体中，这种宿主识别是由位于尾部末端的受体结合蛋白（RBP）进行的。RBP和宿主之间的相互作用是噬菌体感染的触发因素，但对于大多数噬菌体而言，其机制的分子细节尚不清楚。在这里，我们提出了电子低温显微镜（cryo-EM）结构的噬菌体T5 RBPpb 5在复杂的大肠杆菌受体，铁的铁色素转运FhuA。单体RBPb 5位于T5的长柔性尾的末端，并且其与FhuA的不可逆结合使T5感染。对复合物内RBPb 5的结构进行分析，与其AlphaFold 2预测的结构进行比较，并将其拟合到先前确定的与FhuA复合的T5尾尖的图谱中，使我们能够提出RBPb 5受体结合到直纤维的传递机制，启动级联事件，使T5进入DNA排出。重要信息有尾噬菌体特异性识别其细菌宿主，它们的受体结合蛋白（RBP）与位于其猎物表面的蛋白质和/或蛋白质的相互作用。这种至关重要的相互作用使病毒感染，但这种机制的分子细节对于大多数噬菌体来说是未知的。我们测定了T5噬菌体RBPb 5与其E.大肠杆菌受体FhuA。RBP与其蛋白质受体结合的第一个结构使我们能够提出一种将宿主识别传递到噬菌体其余部分的机制，最终打开衣壳并穿透细胞壁，从而使DNA安全地进入宿主细胞质。
Tailed bacteriophages specifically recognize their bacterial host by interaction of their receptor binding protein(s) (RBPs) with saccharides and/or proteins located at the surface of their prey. This crucial interaction commits the virus to infection, but the molecular details of this mechanism are unknown for the majority of bacteriophages.Bacteriophages, viruses infecting bacteria, recognize their host with high specificity, binding to either saccharide motifs or proteins of the cell wall of their host. In the majority of bacteriophages, this host recognition is performed by receptor binding proteins (RBPs) located at the extremity of a tail. Interaction between the RBPs and the host is the trigger for bacteriophage infection, but the molecular details of the mechanisms are unknown for most bacteriophages. Here, we present the electron cryomicroscopy (cryo-EM) structure of bacteriophage T5 RBPpb5 in complex with its Escherichia coli receptor, the iron ferrichrome transporter FhuA. Monomeric RBPpb5 is located at the extremity of T5's long flexible tail, and its irreversible binding to FhuA commits T5 to infection. Analysis of the structure of RBPpb5 within the complex, comparison with its AlphaFold2-predicted structure, and its fit into a previously determined map of the T5 tail tip in complex with FhuA allow us to propose a mechanism of transmission of the RBPpb5 receptor binding to the straight fiber, initiating the cascade of events that commits T5 to DNA ejection.IMPORTANCE Tailed bacteriophages specifically recognize their bacterial host by interaction of their receptor binding protein(s) (RBPs) with saccharides and/or proteins located at the surface of their prey. This crucial interaction commits the virus to infection, but the molecular details of this mechanism are unknown for the majority of bacteriophages. We determined the structure of bacteriophage T5 RBPpb5 in complex with its E. coli receptor, FhuA, by cryo-EM. This first structure of an RBP bound to its protein receptor allowed us to propose a mechanism of transmission of host recognition to the rest of the phage, ultimately opening the capsid and perforating the cell wall and, thus, allowing safe channeling of the DNA into the host cytoplasm.