The type I adenosine 5′-triphosphate (ATP)–binding cassette (ABC) transporter DppABCD is believed to be responsible for the import of exogenous heme as an iron source into the cytoplasm of the human pathogen Mycobacterium tuberculosis (Mtb). Additionally, this system is also known to be involved in the acquisition of tri- or tetra-peptides. Here, we report the cryo–electron microscopy structures of the dual-function Mtb DppABCD transporter in three forms, namely, the apo, substrate-bound, and ATP-bound states. The apo structure reveals an unexpected and previously uncharacterized assembly mode for ABC importers, where the lipoprotein DppA, a cluster C substrate-binding protein (SBP), stands upright on the translocator DppBCD primarily through its hinge region and N-lobe. These structural data, along with biochemical studies, reveal the assembly of DppABCD complex and the detailed mechanism of DppABCD-mediated transport. Together, these findings provide a molecular roadmap for understanding the transport mechanism of a cluster C SBP and its translocator.

中文翻译：

---

结核分枝杆菌 ABC 输入蛋白 DppABCD 底物转运的分子基础

I 型腺苷 5′-三磷酸 (ATP) 结合盒 (ABC) 转运蛋白 DppABCD 被认为负责将外源血红素作为铁源输入人类病原体结核分枝杆菌( Mtb )的细胞质。此外，该系统还参与三肽或四肽的获取。在这里，我们报道了双功能Mtb DppABCD 转运蛋白三种形式的冷冻电子显微镜结构，即apo、底物结合和 ATP 结合状态。 apo结构揭示了ABC输入蛋白的一种意想不到且以前未表征的组装模式，其中脂蛋白 DppA（一种 C 簇底物结合蛋白 (SBP)）主要通过其铰链区和 N 叶在易位子 DppBCD 上直立。这些结构数据以及生化研究揭示了 DppABCD 复合物的组装以及 DppABCD 介导的运输的详细机制。总之，这些发现为理解簇 C SBP 及其转运蛋白的转运机制提供了分子路线图。