Unlocking of the filamentous bacteriophage virion during infection is mediated by the C domain of pill
Unlocking of the filamentous bacteriophage virion during infection is mediated by the C domain of pill
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DOI：
10.1016/j.jmb.2005.11.069
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发表时间：
2006-02-17
影响因子：
5.6
通讯作者：
Rakonjac, J
中科院分区：
文献类型：
--
作者：
Bennett, NJ;Rakonjac, J
丝状噬菌体的蛋白III （pIII）在噬菌体生命周期的开始和结束都是必需的。感染开始于n端N2和N1结构域分别与初级和次级宿主受体F菌毛和TolA蛋白结合，而生命周期结束于c端结构域介导的膜锚定病毒粒子从细胞中释放。据推测，pIII的c端结构域在感染中的作用是将受体结合结构域N1N2连接到病毒粒子的主体。在受体结合后的一个鲜为人知的过程中，当病毒粒子的蛋白质整合到宿主细胞膜上时，病毒粒子就会解体，导致噬菌体基因组进入细菌的细胞质。为了开始揭示这一过程的机制，我们发现通过终止无能的C结构域将功能性N1N2受体结合结构域连接到病毒粒子上可以消除感染。这种感染缺陷不能通过功能性C结构域的反式供应来补充。因此，pIII的C结构域与受体结合结构域协同作用，介导感染中的受体后结合事件。基于这些发现，我们提出了一个模型，其中N1结构域结合到TolA的质周部分，二级受体，顺式触发C结构域的构象变化，这种变化打开或解锁病毒粒子的pIII端，允许感染进入阶段进行。据我们所知，这是第一个使用相同蛋白质结构域插入和释放宿主膜的病毒。(c) 2005 Elsevier Ltd版权所有。
Protein III (pIII) of filamentous phage is required for both the beginning and the end of the phage life cycle. The infection starts by binding of the N-terminal N2 and N1 domains to the primary and secondary host receptors, F pilus and TolA protein, respectively, whereas the life cycle terminates by the C-terminal domain-mediated release of the membrane-anchored virion from the cell. It has been assumed that the role of the C-terminal domain of pIII in the infection is that of a tether for the receptor-binding domains N1N2 to the main body of the virion.In a poorly understood process that follows receptor binding, the virion disassembles as its protein(s) become integrated into the host inner membrane, resulting in the phage genome entry into the bacterial cytoplasm. To begin revealing the mechanism of this process, we showed that tethering the functional N1N2 receptor-binding domain to the virion via termination-incompetent C domain abolishes infection. This infection defect cannot be complemented by in trans supply of the functional C domain. Therefore, the C domain of pIII acts in concert with the receptor-binding domains to mediate the post receptor binding events in the infection.Based on these findings, we propose a model in which binding of the N1 domain to the periplasmic portion of TolA, the secondary receptor, triggers in cis a conformational change in the C domain, and that this change opens or unlocks the pIII end of the virion, allowing the entry phase of infection to proceed.To our knowledge, this is the first virus that uses the same protein domain both for the insertion into and release from the host membrane. (c) 2005 Elsevier Ltd. All rights reserved.