XTAL - Macromolecular Crystallography Laboratory, UCIBIO, Departamento de Química, Faculdade de Ciências E Tecnologia, Universidade NOVA de Lisboa, Quinta da Torre, 2829-516, Caparica, Portugal.
Microbial Genetics Laboratory, UCIBIO, Departamento de Ciências da Vida, Faculdade de Ciências E Tecnologia, Universidade NOVA de Lisboa, Quinta da Torre, 2829-516, Caparica, Portugal.
Sci Rep. 2020 Nov 11;10(1):19564. doi: 10.1038/s41598-020-76444-0.
ATP-binding cassette (ABC) type I importers are widespread in bacteria and play a crucial role in its survival and pathogenesis. They share the same modular architecture comprising two intracellular nucleotide-binding domains (NBDs), two transmembrane domains (TMDs) and a substrate-binding protein. The NBDs bind and hydrolyze ATP, thereby generating conformational changes that are coupled to the TMDs and lead to substrate translocation. A group of multitask NBDs that are able to serve as the cellular motor for multiple sugar importers was recently discovered. To understand why some ABC importers share energy-coupling components, we used the MsmX ATPase from Bacillus subtilis as a model for biological and structural studies. Here we report the first examples of functional hybrid interspecies ABC type I importers in which the NBDs could be exchanged. Furthermore, the first crystal structure of an assigned multitask NBD provides a framework to understand the molecular basis of the broader specificity of interaction with the TMDs.
ATP 结合盒（ABC）型进口商在细菌中广泛存在，在其生存和发病机制中起着至关重要的作用。它们具有相同的模块化结构，包括两个细胞内核苷酸结合域（NBD）、两个跨膜域（TMD）和一个底物结合蛋白。NBD 结合并水解 ATP，从而产生与 TMD 偶联的构象变化，并导致底物易位。最近发现了一组能够作为多种糖进口商的细胞马达的多功能 NBD。为了了解为什么一些 ABC 进口商共享能量偶联组件，我们使用枯草芽孢杆菌的 MsmX ATPase 作为生物和结构研究的模型。在这里，我们报告了第一个功能性杂交种 ABC 型 I 进口商的实例，其中 NBD 可以交换。此外，第一个指定的多功能 NBD 的晶体结构提供了一个框架，以了解与 TMD 相互作用的更广泛特异性的分子基础。
