Center for Disease Control and Prevention of Chinese PLA, Beijing, 100071, China; Academy of Military Medical Sciences, 27(#) Taiping Road, Haidian District, Beijing, 100101, China.
Center for Disease Control and Prevention of Chinese PLA, Beijing, 100071, China; Academy of Military Medical Sciences, 27(#) Taiping Road, Haidian District, Beijing, 100101, China; Comprehensive Liver Cancer Center, 302 Military Hospital, Beijing, China.
Biochem Biophys Res Commun. 2019 Mar 26;511(1):148-153. doi: 10.1016/j.bbrc.2019.01.126. Epub 2019 Feb 14.
Aspergillus fumigatus is a major pathogen of invasive pulmonary aspergillosis with high mortality rate. The nucleoside diphosphate kinase of A. fumigatus, AfNDK (also called SwoH) is essential for its viability, however, its structural characteristic was unknown. In this study, we solved the crystal structure of AfNDK and found that it exists predominantly in form of tetramer in solution. Oligomeric form rather than dimeric form was essential for its kinase activity. The Arg30 and the C terminal amino acids were crucial for dimer-dimer interaction and the viability of A. fumigatus. Mutation V83F might make the secondary structure α5 helix protrude outward so that the whole protein structure became unstable at higher temperature, which might subsequently result to the inviability of A. fumigatus under 44 °C. In conclusion, the crystal structure of AfNDK was for the first time analyzed and the stability of the tetrameric form with dimer-dimer interaction were crucial for its function in A. fumigatus.
烟曲霉是一种主要的侵袭性肺曲霉病病原体，死亡率很高。烟曲霉的核苷二磷酸激酶，AfNDK（也称为 SwoH）对其生存能力至关重要，但它的结构特征尚不清楚。在这项研究中，我们解析了 AfNDK 的晶体结构，发现它在溶液中主要以四聚体的形式存在。寡聚形式而不是二聚体形式对于其激酶活性是必需的。Arg30 和 C 末端氨基酸对于二聚体-二聚体相互作用和烟曲霉的生存能力至关重要。V83F 突变可能使二级结构α5 螺旋向外突出，从而使整个蛋白质结构在较高温度下变得不稳定，这可能导致烟曲霉在 44°C 下无法生存。总之，首次对 AfNDK 的晶体结构进行了分析，二聚体-二聚体相互作用的四聚体形式的稳定性对于其在烟曲霉中的功能至关重要。
