Bacteriophage Medical Research Center, Department of Biology, The Catholic University of America, Washington, DC 20064, USA.
Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.
Viruses. 2023 Feb 14;15(2):527. doi: 10.3390/v15020527.
Bacteriophage (phage) T4 has served as an extraordinary model to elucidate biological structures and mechanisms. Recent discoveries on the T4 head (capsid) structure, portal vertex, and genome packaging add a significant body of new literature to phage biology. Head structures in unexpanded and expanded conformations show dramatic domain movements, structural remodeling, and a ~70% increase in inner volume while creating high-affinity binding sites for the outer decoration proteins Soc and Hoc. Small changes in intercapsomer interactions modulate angles between capsomer planes, leading to profound alterations in head length. The in situ cryo-EM structure of the symmetry-mismatched portal vertex shows the remarkable structural morphing of local regions of the portal protein, allowing similar interactions with the capsid protein in different structural environments. Conformational changes in these interactions trigger the structural remodeling of capsid protein subunits surrounding the portal vertex, which propagate as a wave of expansion throughout the capsid. A second symmetry mismatch is created when a pentameric packaging motor assembles at the outer "clip" domains of the dodecameric portal vertex. The single-molecule dynamics of the packaging machine suggests a continuous burst mechanism in which the motor subunits adjusted to the shape of the DNA fire ATP hydrolysis, generating speeds as high as 2000 bp/s.
噬菌体（phage）T4 一直是阐明生物学结构和机制的极佳模型。最近关于 T4 头部（衣壳）结构、门户顶点和基因组包装的发现，为噬菌体生物学增添了大量新的文献。在未扩展和扩展构象中的头部结构显示出剧烈的结构运动、结构重塑以及内体积增加约 70%，同时为外壳蛋白 Soc 和 Hoc 创造了高亲和力结合位点。衣壳蛋白间相互作用的微小变化调节衣壳蛋白平面之间的角度，导致头部长度发生深刻变化。对称性不匹配门户顶点的原位 cryo-EM 结构显示出门户蛋白局部区域的惊人结构变形，允许在不同的结构环境中与衣壳蛋白进行类似的相互作用。这些相互作用的构象变化触发围绕门户顶点的衣壳蛋白亚基的结构重塑，该重塑作为扩张波在整个衣壳中传播。当五聚体包装机制在十二聚体门户顶点的外部“夹子”域组装时，会产生第二个对称性不匹配。包装机的单分子动力学表明，存在连续爆发机制，其中马达亚基适应 DNA 的形状，引发 ATP 水解，产生高达 2000 bp/s 的速度。
