Rosa Leonardo Talachia, Vernhes Émeline, Soulet Anne-Lise, Polard Patrice, Fronzes Rémi
Structure and Function of Bacterial Nanomachines-Institut Européen de Chimie et Biologie, Microbiologie fondamentale et pathogénicité, UMR 5234, CNRS, University of Bordeaux, 2 rue Robert Escarpit, 33600, Pessac, France.
Departamento de Bioquímica e Biologia Tecidual. Laboratório de Bioquímica de Complexos Bacterianos. Instituto de Biologia. Universidade Estadual de Campinas (UNICAMP), Monteiro Lobato, 255, Campinas, 13083-862, Brasil.
EMBO J. 2024 Dec;43(23):6180-6198. doi: 10.1038/s44318-024-00264-5. Epub 2024 Oct 18.
Some DNA helicases play central and specific roles in genome maintenance and plasticity through their branch migration activity in different pathways of homologous recombination. RadA is a highly conserved bacterial helicase involved in DNA repair throughout all bacterial species. In Gram-positive Firmicutes, it also has a role in natural transformation, while in Gram-negative bacteria, ComM is the canonical transformation-specific helicase. Both RadA and ComM helicases form hexameric rings and use ATP hydrolysis as an energy source to propel themselves along DNA. In this study, we present the cryoEM structures of RadA and ComM interacting with DNA and ATP analogs. These structures reveal important molecular interactions that couple ATP hydrolysis and DNA binding in RadA, as well as the role of the Lon protease-like domain, shared by RadA and ComM, in this process. Taken together, these results provide new molecular insights into the mechanisms of DNA branch migration in different pathways of homologous recombination.
一些DNA解旋酶通过在同源重组的不同途径中的分支迁移活性，在基因组维持和可塑性中发挥核心和特定作用。RadA是一种高度保守的细菌解旋酶，参与所有细菌物种的DNA修复。在革兰氏阳性厚壁菌门中，它在自然转化中也发挥作用，而在革兰氏阴性细菌中，ComM是典型的转化特异性解旋酶。RadA和ComM解旋酶都形成六聚体环，并利用ATP水解作为能量来源沿DNA推进。在本研究中，我们展示了RadA和ComM与DNA及ATP类似物相互作用的冷冻电镜结构。这些结构揭示了在RadA中耦合ATP水解和DNA结合的重要分子相互作用，以及RadA和ComM共有的Lon蛋白酶样结构域在此过程中的作用。综上所述，这些结果为同源重组不同途径中DNA分支迁移的机制提供了新的分子见解。
