英国MRC分子生物学结构研究实验室Jan Löwe团队发现了MukBEF SMC复合物捕获DNA的机制及其被病毒DNA模拟物抑制。2025年3月31日出版的《细胞》发表了这项成果。

该研究组探索了细菌SMC复合体MukBEF的DNA加载过程。利用低温电子显微镜（cryo-EM），研究组证明ATP结合打开了MukBEF的三个潜在DNA进入门之一，暴露出DNA捕获位点，将DNA定位在打开的颈门。该课题组发现噬菌体T7的gp5.9蛋白通过DNA模拟阻断这个捕获位点，从而阻止DNA装载并使MukBEF失活。该课题组人员提出了一种全面的单向加载机制，其中DNA首先在复合物的外围被捕获，然后通过DNA入口门被摄取，由ATP水解的单周期提供动力。这些发现阐明了泛素DNA组织者如何为基因组维护做好准备的一个基本方面，并证明了这一过程如何被病毒主题破坏。

据悉，染色体环状结构维持（SMC）复合体在基因组组织中起着至关重要的作用，其作用机制包括DNA包裹和环外脱。

附：英文原文

Title: Mechanism of DNA capture by the MukBEF SMC complex and its inhibition by a viral DNA mimic

Author: Frank Bürmann, Bryony Clifton, Sophie Koekemoer, Oliver J. Wilkinson, Dari Kimanius, Mark S. Dillingham, Jan Lwe

Issue&Volume: 2025-03-31

Abstract: Ring-like structural maintenance of chromosome (SMC) complexes are crucial for genome organization and operate through mechanisms of DNA entrapment and loop extrusion. Here, we explore the DNA loading process of the bacterial SMC complex MukBEF. Using cryoelectron microscopy (cryo-EM), we demonstrate that ATP binding opens one of MukBEF’s three potential DNA entry gates, exposing a DNA capture site that positions DNA at the open neck gate. We discover that the gp5.9 protein of bacteriophage T7 blocks this capture site by DNA mimicry, thereby preventing DNA loading and inactivating MukBEF. We propose a comprehensive and unidirectional loading mechanism in which DNA is first captured at the complex’s periphery and then ingested through the DNA entry gate, powered by a single cycle of ATP hydrolysis. These findings illuminate a fundamental aspect of how ubiquitous DNA organizers are primed for genome maintenance and demonstrate how this process can be disrupted by viruses.

DOI: 10.1016/j.cell.2025.02.032

Source: https://www.cell.com/cell/abstract/S0092-8674(25)00259-4