Li Xiaolu, Zhuo Wei, Yu Jie, Ge Jingpeng, Gu Jinke, Feng Yue, Yang Maojun, Wang Linfang, Wang Na
State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Tsinghua University, Beijing 100005, People's Republic of China.
Acta Crystallogr D Biol Crystallogr. 2013 Feb;69(Pt 2):256-65. doi: 10.1107/S0907444912045180. Epub 2013 Jan 19.
Dipeptide permease (Dpp), which belongs to an ABC transport system, imports peptides consisting of two or three L-amino acids from the matrix to the cytoplasm in microbes. Previous studies have indicated that haem competes with dipeptides to bind DppA in vitro and in vivo and that the Dpp system can also translocate haem. Here, the crystal structure of DppD, the nucleotide-binding domain (NBD) of the ABC-type dipeptide/oligopeptide/nickel-transport system from Thermoanaerobacter tengcongensis, bound with ATP, Mg(2+) and a [4Fe-4S] iron-sulfur cluster is reported. The N-terminal domain of DppD shares a similar structural fold with the NBDs of other ABC transporters. Interestingly, the C-terminal domain of DppD contains a [4Fe-4S] cluster. The UV-visible absorbance spectrum of DppD was consistent with the presence of a [4Fe-4S] cluster. A search with DALI revealed that the [4Fe-4S] cluster-binding domain is a novel structural fold. Structural analysis and comparisons with other ABC transporters revealed that this iron-sulfur cluster may act as a mediator in substrate (dipeptide or haem) binding by electron transfer and may regulate the transport process in Dpp ABC transport systems. The crystal structure provides a basis for understanding the properties of ABC transporters and will be helpful in investigating the functions of NBDs in the regulation of ABC transporter activity.
二肽通透酶（Dpp）属于ABC转运系统，可将由两个或三个L-氨基酸组成的肽从微生物的基质转运至细胞质中。先前的研究表明，血红素在体外和体内均与二肽竞争结合DppA，并且Dpp系统也能转运血红素。在此，报道了嗜热栖热放线菌ABC型二肽/寡肽/镍转运系统的核苷酸结合结构域（NBD）DppD与ATP、Mg(2+)和[4Fe-4S]铁硫簇结合的晶体结构。DppD的N端结构域与其他ABC转运蛋白的NBD具有相似的结构折叠。有趣的是，DppD的C端结构域包含一个[4Fe-4S]簇。DppD的紫外可见吸收光谱与存在[4Fe-4S]簇一致。用DALI搜索发现，[4Fe-4S]簇结合结构域是一种新颖的结构折叠。结构分析以及与其他ABC转运蛋白的比较表明，这种铁硫簇可能通过电子转移作为底物（二肽或血红素）结合的介质，并可能调节Dpp ABC转运系统中的转运过程。该晶体结构为理解ABC转运蛋白的特性提供了基础，将有助于研究NBD在调节ABC转运蛋白活性中的功能。
