Modeling the Architecture of Depolymerase-Containing Receptor Binding Proteins in Klebsiella Phages
Modeling the Architecture of Depolymerase-Containing Receptor Binding Proteins in Klebsiella Phages
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DOI：
10.3389/fmicb.2019.02649
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发表时间：
2019-11-15
影响因子：
5.2
通讯作者：
Briers, Yves
中科院分区：
文献类型：
--
作者：
Latka, Agnieszka;Leiman, Petr G.;Briers, Yves
肺炎克雷伯菌携带一层厚厚的多糖囊。这种高度可变的化学结构在其毒力中起着重要作用。许多克雷伯氏菌噬菌体用含有解聚合酶结构域的受体结合蛋白（RBP）识别这种胶囊。该结构域降解荚膜以引发噬菌体感染。rbp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。大多数已知的克雷伯氏菌噬菌体只有一个或两个rbp，但已确定具有多达11个rbp的噬菌体具有解聚合酶活性和广泛的宿主谱。详细的生物信息学分析表明，类似的RBP结构域在肺炎克氏菌噬菌体中反复出现，具有结构RBP结构域，用于RBP附着在噬菌体尾部（锚定结构域）或RBP分支（t4gp10样结构域）。决定RBP结构的结构域位于蛋白质的n端，而解聚合酶位于蛋白质的中心。偶尔，RBP在远端有一个可自动切割的伴侣结构域，用于折叠和多聚。酶结构域受到强烈的水平转移以快速转移噬菌体宿主谱而不影响RBP结构。这些分析允许对一组保守的RBP结构进行建模，表明进化联系。
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.