Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, School of Medicine, Aurora, USA.
Commun Biol. 2021 Dec 9;4(1):1383. doi: 10.1038/s42003-021-02916-2.
As one of the most elegant biological processes developed in bacteria, the siderophore-mediated iron uptake demands the action of specific ATP-binding cassette (ABC) importers. Although extensive studies have been done on various ABC importers, the molecular basis of these iron-chelated-siderophore importers are still not fully understood. Here, we report the structure of a ferrichrome importer FhuCDB from Escherichia coli at 3.4 Å resolution determined by cryo electron microscopy. The structure revealed a monomeric membrane subunit of FhuB with a substrate translocation pathway in the middle. In the pathway, there were unique arrangements of residues, especially layers of methionines. Important residues found in the structure were interrogated by mutagenesis and functional studies. Surprisingly, the importer's ATPase activity was decreased upon FhuD binding, which deviated from the current understanding about bacterial ABC importers. In summary, to the best of our knowledge, these studies not only reveal a new structural twist in the type II ABC importer subfamily, but also provide biological insights in the transport of iron-chelated siderophores.
作为细菌中发展起来的最优雅的生物过程之一，铁载体介导的铁摄取需要特定的三磷酸腺苷结合盒（ABC）转运体的作用。尽管已经对各种 ABC 转运体进行了广泛的研究，但这些铁螯合-铁载体转运体的分子基础仍未完全理解。在这里，我们报道了大肠杆菌 ferrichrome 转运体 FhuCDB 的结构，其晶体电子显微镜分辨率为 3.4 Å。该结构揭示了 FhuB 的单体膜亚基，其中间有一个底物转运途径。在该途径中，存在独特的残基排列，特别是层状的蛋氨酸。通过突变和功能研究检测到结构中的重要残基。令人惊讶的是，FhuD 结合后转运体的 ATP 酶活性降低，这与目前对细菌 ABC 转运体的理解不同。总之，据我们所知，这些研究不仅揭示了 II 型 ABC 转运体亚家族的一个新的结构扭曲，还为铁螯合铁载体的转运提供了生物学见解。
