Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Structure. 2012 Aug 8;20(8):1384-90. doi: 10.1016/j.str.2012.05.011. Epub 2012 Jun 28.
Bacteriophage HK97 maturation involves discrete intermediate particle forms, comparable to transitional states in protein folding, before reaching its mature form. The process starts by formation of a metastable prohead, poised for exothermic expansion triggered by DNA packaging. During maturation, the capsid subunit transitions from a strained to a canonical tertiary conformation and this has been postulated to be the driving mechanism for initiating expansion via switching hexameric capsomer architecture from skewed to 6-fold symmetric. We report the subnanometer electron-cryomicroscopy reconstruction of the HK97 first expansion intermediate before any crosslink formation. This form displays 6-fold symmetric hexamers, but capsid subunit tertiary structures exhibit distortions comparable to the prohead forms. We propose that coat subunit strain release acts in synergy with the first crosslinks to drive forward maturation. Finally, we speculate that the energetic features of this transition may result from increased stability of intermediates during maturation via enhanced inter-subunit interactions.
噬菌体 HK97 的成熟过程涉及离散的中间颗粒形式，类似于蛋白质折叠中的过渡态，然后才能达到成熟形式。该过程首先通过形成亚稳态头部开始，准备好通过 DNA 包装触发的放热膨胀。在成熟过程中，衣壳亚基从应变状态转变为规范的三级构象，据推测这是通过将六聚体衣壳结构从倾斜转变为 6 重对称来启动扩张的驱动机制。我们报告了 HK97 的第一个膨胀中间产物的亚纳米电子低温显微镜重建，在此之前没有形成任何交联。这种形式显示出 6 重对称的六聚体，但衣壳亚基三级结构显示出与头部形式相当的扭曲。我们提出，外壳亚基应变释放与第一个交联协同作用，推动成熟过程。最后，我们推测这种转变的能量特征可能是由于成熟过程中通过增强亚基间相互作用增加了中间体的稳定性所致。
