Trokter Martina, Felisberto-Rodrigues Catarina, Christie Peter J, Waksman Gabriel
Institute of Structural and Molecular Biology, University College London and Birkbeck, Malet Street, London WC1E 7HX, UK.
Department of Microbiology and Molecular Genetics, University of Texas Medical School, 6431 Fannin Street, Houston, TX 77030, USA.
Curr Opin Struct Biol. 2014 Aug;27:16-23. doi: 10.1016/j.sbi.2014.02.006. Epub 2014 Apr 5.
Bacteria use type IV secretion (T4S) systems to deliver DNA and protein substrates to a diverse range of prokaryotic and eukaryotic target cells. T4S systems have great impact on human health, as they are a major source of antibiotic resistance spread among bacteria and are central to infection processes of many pathogens. Therefore, deciphering the structure and underlying translocation mechanism of T4S systems is crucial to facilitate development of new drugs. The last five years have witnessed considerable progress in unraveling the structure of T4S system subassemblies, notably that of the T4S system core complex, a large 1 MegaDalton (MDa) structure embedded in the double membrane of Gram-negative bacteria and made of 3 of the 12 T4S system components. However, the recent determination of the structure of -3MDa assembly of 8 of these components has revolutionized our views of T4S system architecture and opened up new avenues of research, which are discussed in this review.
细菌利用IV型分泌(T4S)系统将DNA和蛋白质底物传递给各种原核和真核靶细胞。T4S系统对人类健康有重大影响,因为它们是细菌间抗生素耐药性传播的主要来源,并且在许多病原体的感染过程中起着核心作用。因此,解析T4S系统的结构及其潜在的转运机制对于促进新药开发至关重要。在过去五年中,在揭示T4S系统子组件的结构方面取得了相当大的进展,特别是T4S系统核心复合物的结构,这是一种嵌入革兰氏阴性菌双膜中的大型1兆道尔顿(MDa)结构,由12个T4S系统组件中的3个组成。然而,最近对其中8个组件的-3MDa组装体结构的测定彻底改变了我们对T4S系统结构的看法,并开辟了新的研究途径,本综述将对此进行讨论。