Structure and infection dynamics of mycobacteriophage Bxb1

IF 45.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cell Pub Date : 2025-04-15 DOI:10.1016/j.cell.2025.03.027

Krista G. Freeman, Sudipta Mondal, Lourriel S. Macale, Jennifer Podgorski, Simon J. White, Benjamin H. Silva, Valery Ortiz, Alexis Huet, Ronelito J. Perez, Joemark T. Narsico, Meng-Chiao Ho, Deborah Jacobs-Sera, Todd L. Lowary, James F. Conway, Donghyun Park, Graham F. Hatfull

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引用次数: 0

Abstract

Mycobacteriophage Bxb1 is a well-characterized virus of Mycobacterium smegmatis with double-stranded DNA and a long, flexible tail. Mycobacteriophages show considerable potential as therapies for Mycobacterium infections, but little is known about the structural details of these phages or how they bind to and traverse the complex Mycobacterium cell wall. Here, we report the complete structure and atomic model of phage Bxb1, including the arrangement of immunodominant domains of both the capsid and tail tube subunits, as well as the assembly of the protein subunits in the tail-tip complex. The structure contains protein assemblies with 3-, 5-, 6-, and 12-fold symmetries, which interact to satisfy several symmetry mismatches. Cryoelectron tomography of phage particles bound to M. smegmatis reveals the structural transitions that occur for free phage particles to bind to the cell surface and navigate through the cell wall to enable DNA transfer into the cytoplasm.

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噬菌体 Bxb1 的结构和感染动力学

分枝噬菌体Bxb1是耻垢分枝杆菌的一种具有良好特征的病毒，具有双链DNA和长而灵活的尾巴。分枝杆菌噬菌体在治疗分枝杆菌感染方面显示出相当大的潜力，但对这些噬菌体的结构细节或它们如何结合和穿过复杂的分枝杆菌细胞壁知之甚少。在这里，我们报道了噬菌体Bxb1的完整结构和原子模型，包括衣壳和尾管亚基的免疫优势结构域的排列，以及蛋白亚基在尾尖复合物中的组装。该结构包含3倍、5倍、6倍和12倍对称的蛋白质组合，它们相互作用以满足几种对称不匹配。与耻垢分枝杆菌结合的噬菌体颗粒的低温电子断层扫描揭示了自由噬菌体颗粒与细胞表面结合并穿过细胞壁以使DNA转移到细胞质中所发生的结构转变。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell 生物-生化与分子生物学

CiteScore

110.00

自引率

0.80%

发文量

396

审稿时长

2 months

期刊介绍： Cells is an international, peer-reviewed, open access journal that focuses on cell biology, molecular biology, and biophysics. It is affiliated with several societies, including the Spanish Society for Biochemistry and Molecular Biology (SEBBM), Nordic Autophagy Society (NAS), Spanish Society of Hematology and Hemotherapy (SEHH), and Society for Regenerative Medicine (Russian Federation) (RPO). The journal publishes research findings of significant importance in various areas of experimental biology, such as cell biology, molecular biology, neuroscience, immunology, virology, microbiology, cancer, human genetics, systems biology, signaling, and disease mechanisms and therapeutics. The primary criterion for considering papers is whether the results contribute to significant conceptual advances or raise thought-provoking questions and hypotheses related to interesting and important biological inquiries. In addition to primary research articles presented in four formats, Cells also features review and opinion articles in its "leading edge" section, discussing recent research advancements and topics of interest to its wide readership.