Phage tail fibre assembly proteins employ a modular structure to drive the correct folding of diverse fibres
Phage tail fibre assembly proteins employ a modular structure to drive the correct folding of diverse fibres
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DOI：
10.1038/s41564-019-0477-7
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发表时间：
2019-06
影响因子：
28.3
通讯作者：
Olesia I. North;Kouhei Sakai;E. Yamashita;A. Nakagawa;T. Iwazaki;Carina R. Büttner;S. Takeda;A. Davidson
中科院分区：
文献类型：
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作者：
Olesia I. North;Kouhei Sakai;E. Yamashita;A. Nakagawa;T. Iwazaki;Carina R. Büttner;S. Takeda;A. Davidson
噬菌体尾部纤维是细长的蛋白质组合，能够在病毒感染的第一步特异性识别细菌表面，，-。这些复杂的三聚体结构的折叠通常需要噬菌体编码的尾部纤维组装（Tfa）蛋白-。尽管Tfa蛋白广泛存在，但其功能机制尚未阐明。本文研究了大肠杆菌噬菌体的尾部纤维和Tfa。我们证明了Tfa与尾纤维形成稳定的配合物，并给出了该配合物的2.1 Å分辨率的x射线晶体结构。我们发现Tfa蛋白由两个结构域组成：一个非保守的n端结构域与纤维的c端区域结合，一个保守的c端结构域可能介导纤维的寡聚化和组装。Tfa本身形成快速交换的多聚体，但不是稳定的三聚体，这意味着Tfa不能指定纤维的三聚体状态。我们提出Tfa的关键保守作用是确保纤维组装和多聚在C端启动，确保纤维的缠绕和重复结构元件以正确的顺序聚集在一起。我们的工作强调了正确排列噬菌体纤维C端的普遍重要性。
Phage tail fibres are elongated protein assemblies capable of specific recognition of bacterial surfaces during the first step of viral infection, , –. The folding of these complex trimeric structures often requires a phage-encoded tail fibre assembly (Tfa) protein, –. Despite the wide occurrence of Tfa proteins, their functional mechanism has not been elucidated. Here, we investigate the tail fibre and Tfa ofEscherichia coliphage Mu. We demonstrate that Tfa forms a stable complex with the tail fibre, and present a 2.1 Å resolution X-ray crystal structure of this complex. We find that Tfa proteins are comprised of two domains: a non-conserved N-terminal domain that binds to the C-terminal region of the fibre and a conserved C-terminal domain that probably mediates fibre oligomerization and assembly. Tfa forms rapidly exchanging multimers on its own, but not a stable trimer, implying that Tfa does not specify the trimeric state of the fibre. We propose that the key conserved role of Tfa is to ensure that fibre assembly and multimerization initiates at the C terminus, ensuring that the intertwined and repetitive structural elements of fibres come together in the correct sequence. The universal importance of correctly aligning the C termini of phage fibres is highlighted by our work.