目前细菌耐药性问题日益严重，甚至出现了“超级细菌”，对人类健康产生了严重威胁。现有的抗生素无法抵抗这些“超级细菌”，急需探寻新的治疗途径。噬菌体治疗作为一种抗生素替代物，具有特异性强、对人体无害、生产周期短等优点，目前已有临床成功的案例，展现出了巨大的潜力。但是目前关于噬菌体侵染机制尤其是长尾噬菌体的侵染机制还知之甚少，关于噬菌体的组装机制也有很多问题没有解决，限制了噬菌体治疗的进一步发展。Lambda噬菌体作为研究噬菌体组装的经典模型，研究清楚它的组装机制对于研究其他具有HK97折叠的噬菌体具有重要意义。同时lambda噬菌体作为长尾噬菌体科的典型代表，研究清楚其侵染机制对于其他长尾噬菌体侵染机制的研究也有借鉴意义。 本文研究中我们解析了分辨率为5.0 ?的lambda噬菌体前体衣壳结构，分辨率为5.6 ?的lambda噬菌体成熟衣壳结构，分辨率为3.8 ?的lambda噬菌体前体衣壳二十面体基本组成单元的结构，分辨率为3.7 ?的lambda噬菌体成熟衣壳二十面体基本组成单元的结构。基于以上结构数据具体分析了lambda噬菌体衣壳成熟过程中的结构变化及机制，完善了噬菌体组装过程研究。我们发现在噬菌体成熟过程中五聚体和六聚体像飞盘一样展开，E-loop及N-arm形成三股β链，顶点处添加粘合蛋白gpD进一步稳定成熟衣壳的结构以抵抗DNA泵入产生的内部压力。 除此之外，为了研究清楚lambda噬菌体尾部组装机制及侵染机制，我们首次解析了lambda噬菌体尾部尖端复合物的结构，分辨率为2.5 ?。我们发现lambda噬菌体尾部的gpJ、gpI、gpH蛋白对于噬菌体侵染及DNA传输到宿主大肠杆菌中具有重要作用。据此我们构建了lambda噬菌体侵染机制模型，同时推进了lambda噬菌体尾部组装过程研究。我们认为蛋白gpI的两条疏水螺旋TM1和TM2会插入细菌外膜形成跨膜通道。然后蛋白gpH的C端滑动穿过跨膜通道，并拖动gpH的N端打开尾管的塞子。之后，病毒DNA通过尾管中的孔道进入宿主细胞进行复制。目前对于长尾噬菌体侵染机制相关的结构研究还十分有限，本文的研究结果对于长尾噬菌体侵染机制研究具有重要的开创及拓展意义。 本研究解决了与lambda噬菌体组装及侵染相关的问题，对该领域的研究做出了重要贡献。

At present, the problem of bacterial resistance is becoming more and more serious. The emergence of "super bacteria" posed a serious threat to human health. Existing antibiotics cannot fight these "super bacteria", and new treatments are urgently needed. As an antibiotic substitute, phage therapy has the advantages of strong specificity, no harm to human body, and short production cycle. At present, there have been some successful cases, showing great potential. However, little is known about the infection mechanism of bacteriophage, especially the infection mechanism of Siphoviridae. Many questions about the assembly mechanism of bacteriophage have not been solved, which limits the further development of bacteriophage therapy. As a classical model for studying phage assembly, understanding the assembly mechanism of bacteriophage lambda is of great significance for studying other phages with HK97 fold. As a typical representative of Siphoviridae, understanding the infection mechanism of bacteriophage lambda can also provide reference for the study of the infection mechanism of other phages.In this study, we had resolved the bacteriophage lambda procapsid structure at 5.0 ? resolution, the mature capsid structure at 5.6 ? resolution, the icosahedral asymmetric unit (ASU) of the procapsid at 3.8 ? resolution, the icosahedral asymmetric unit (ASU) of the mature capsid at 3.7 ? resolution. Based on the structural data, the structural changes and mechanisms during the maturation of bacteriophage lambda capsid were analyzed. And the phage assembly process was improved. The pentamer and hexamer rotated like flying swings during phage maturation. And the E-loop and N-arm formed a three-stranded β-sheet. Protein gpD was added at the apex to further stabilize the mature capsid structure to resist the internal pressure caused by DNA pumping.In addition, the structure of the bacteriophage tail tip complex was resolved at 2.5 ? resolution to clarify the mechanism of bacteriophage infection and assembly. The gpJ, gpI and gpH proteins of bacteriophage lambda tail play important roles in phage infection and DNA delivery to the host Escherichia coli. Therefore, a model of the infection mechanism of bacteriophage lambda was constructed and the tail assembly process of bacteriophage lambda was improved. We proposed that the two hydrophobic helices of the protein gpI, TM1 and TM2, will insert into the bacterial outer membrane to form transmembrane channels. The C terminus of the protein gpH slides across the transmembrane channel and drags the N terminus of gpH to open the plug of the tail tube. After that, the viral DNA enters the host cell through the pore in the tail tube for replication. At present, the structural studies related to the infection mechanism of long-tailed phage are still very limited. The results of this study have important significance for the development of the whole study on the infection mechanism of Siphoviridae.This study has solved several problems about bacteriophage lambda assembly and infection. This study makes an important contribution to this field.