CryoEM structure of the outer membrane secretin channel pIV from the f1 filamentous bacteriophage.

CryoEM structure of the outer membrane secretin channel pIV from the f1 filamentous bacteriophage.
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DOI:
10.1038/s41467-021-26610-3
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发表时间:
2021-11-02
影响因子:
16.6
通讯作者:
Gold VAM
Gold VAM
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Conners R;McLaren M;Łapińska U;Sanders K;Stone MRL;Blaskovich MAT;Pagliara S;Daum B;Rakonjac J;Gold VAM

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丝状噬菌体的Ff家族感染革兰氏阴性细菌,但不引起其宿主细胞的裂解。相反,新的病毒体通过噬菌体编码的pIV蛋白被挤出,该蛋白与细菌分泌素具有同源性。在这里,我们确定的结构pIV从f1丝状噬菌体在2.7 μ m的分辨率通过冷冻电子显微镜,第一个近原子结构的噬菌体分泌素。15个f1 pIV亚基在细菌外膜中组装形成门控通道,相关的可溶性结构域投射到周质中。我们模拟通道开放,并提出了一种机制,噬菌体出口。通过单细胞微流体实验,我们证明了分泌素如pIV作为佐剂增加细菌对抗生素的吸收和功效的潜力。最后,我们比较了f1 pIV结构,其同系物,揭示噬菌体和细菌分泌素之间的相似性和差异。Ff噬菌体的新病毒体通过由噬菌体蛋白pIV构建的通道从宿主细胞中挤出,所述噬菌体蛋白pIV与细菌分泌素同源。在这里,作者报道了来自f1丝状噬菌体的这种通道的结构,并提出将其用作佐剂来增加抗生素的吸收和功效。
The Ff family of filamentous bacteriophages infect gram-negative bacteria, but do not cause lysis of their host cell. Instead, new virions are extruded via the phage-encoded pIV protein, which has homology with bacterial secretins. Here, we determine the structure of pIV from the f1 filamentous bacteriophage at 2.7 Å resolution by cryo-electron microscopy, the first near-atomic structure of a phage secretin. Fifteen f1 pIV subunits assemble to form a gated channel in the bacterial outer membrane, with associated soluble domains projecting into the periplasm. We model channel opening and propose a mechanism for phage egress. By single-cell microfluidics experiments, we demonstrate the potential for secretins such as pIV to be used as adjuvants to increase the uptake and efficacy of antibiotics in bacteria. Finally, we compare the f1 pIV structure to its homologues to reveal similarities and differences between phage and bacterial secretins. New virions of Ff bacteriophages are extruded from the host cell via the channel built from phage protein pIV, homologous to bacterial secretins. Here, the authors report the structure of this channel from the f1 filamentous bacteriophage and propose its use as an adjuvant to increase the uptake and efficacy of antibiotics.
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