Table_1_Modeling the Architecture of Depolymerase-Containing Receptor Binding Proteins in Klebsiella Phages.pdf

Klebsiella pneumoniae carries a thick polysaccharide capsule. This highly variable chemical structure plays an important role in its virulence. Many Klebsiella bacteriophages recognize this capsule with a receptor binding protein (RBP) that contains a depolymerase domain. This domain degrades the capsule to initiate phage infection. RBPs are highly specific and thus largely determine the host spectrum of the phage. A majority of known Klebsiella phages have only one or two RBPs, but phages with up to 11 RBPs with depolymerase activity and a broad host spectrum have been identified. A detailed bioinformatic analysis shows that similar RBP domains repeatedly occur in K. pneumoniae phages with structural RBP domains for attachment of an RBP to the phage tail (anchor domain) or for branching of RBPs (T4gp10-like domain). Structural domains determining the RBP architecture are located at the N-terminus, while the depolymerase is located in the center of protein. Occasionally, the RBP is complemented with an autocleavable chaperone domain at the distal end serving for folding and multimerization. The enzymatic domain is subjected to an intense horizontal transfer to rapidly shift the phage host spectrum without affecting the RBP architecture. These analyses allowed to model a set of conserved RBP architectures, indicating evolutionary linkages.

肺炎克雷伯菌（Klebsiella pneumoniae）携带一层厚实的多糖荚膜，其化学结构高度可变，在该菌的致病毒力中发挥关键作用。多数克雷伯菌噬菌体通过携带解聚酶结构域的受体结合蛋白（Receptor Binding Protein，RBP）识别该荚膜，该结构域可降解荚膜以启动噬菌体感染进程。受体结合蛋白具有高度特异性，因此在很大程度上决定了噬菌体的宿主谱。目前已知的多数克雷伯菌噬菌体仅携带1至2种受体结合蛋白，但现已发现部分噬菌体可携带多达11种具备解聚酶活性的受体结合蛋白，且拥有宽泛的宿主谱。详尽的生物信息学分析显示，相似的受体结合蛋白结构域在肺炎克雷伯菌噬菌体中反复出现，这些结构域可分为两类：一类用于将受体结合蛋白锚定至噬菌体尾部（锚定结构域），另一类用于受体结合蛋白的分支延伸（T4gp10样结构域）。决定受体结合蛋白整体架构的结构域位于其N末端，而解聚酶结构域则位于蛋白的中部区域。部分受体结合蛋白在其远端还附带一个自剪切伴侣结构域，用于介导蛋白折叠与多聚化过程。该酶结构域经历了频繁的水平基因转移，使得噬菌体能够在不改变受体结合蛋白整体架构的前提下，快速调整其宿主谱。上述分析得以构建出一套保守的受体结合蛋白架构模型，揭示了其间的进化关联。