趋化因子XCL1抗菌活性中变质相互转化的要求。
A Requirement for Metamorphic Interconversion in the Antimicrobial Activity of Chemokine XCL1.
作者信息
Nevins Amanda M, Subramanian Akshay, Tapia Jazma L, Delgado David P, Tyler Robert C, Jensen Davin R, Ouellette André J, Volkman Brian F
机构信息
Department of Biochemistry, Medical College of Wisconsin , Milwaukee, Wisconsin 53226, United States.
Department of Pathology and Laboratory Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California , Los Angeles, California 90089, United States.
出版信息
Biochemistry. 2016 Jul 12;55(27):3784-93. doi: 10.1021/acs.biochem.6b00353. Epub 2016 Jun 28.
Chemokines make up a superfamily of ∼50 small secreted proteins (8-12 kDa) involved in a host of physiological processes and disease states, with several previously shown to have direct antimicrobial activity comparable to that of defensins in efficacy. XCL1 is a unique metamorphic protein that interconverts between the canonical chemokine fold and a novel all-β-sheet dimer. Phylogenetic analysis suggests that, within the chemokine family, XCL1 is most closely related to CCL20, which exhibits antibacterial activity. The in vitro antimicrobial activity of WT-XCL1 and structural variants was quantified using a radial diffusion assay (RDA) and in solution bactericidal assays against Gram-positive and Gram-negative species of bacteria. Comparisons of WT-XCL1 with variants that limit metamorphic interconversion showed a loss of antimicrobial activity when restricted to the conserved chemokine fold. These results suggest that metamorphic folding of XCL1 is required for potent antimicrobial activity.
趋化因子构成了一个超家族，由约50种小分泌蛋白（8 - 12 kDa）组成，参与许多生理过程和疾病状态，此前有几种趋化因子已显示出具有与防御素相当的直接抗菌活性。XCL1是一种独特的变构蛋白，可在典型趋化因子折叠和一种新型全β - 折叠二聚体之间相互转换。系统发育分析表明，在趋化因子家族中，XCL1与具有抗菌活性的CCL20关系最为密切。使用径向扩散测定法（RDA）以及针对革兰氏阳性和革兰氏阴性细菌的溶液杀菌测定法对野生型XCL1和结构变体的体外抗菌活性进行了量化。将野生型XCL1与限制变构相互转换的变体进行比较，结果显示当局限于保守的趋化因子折叠时，抗菌活性丧失。这些结果表明，XCL1的变构折叠是强效抗菌活性所必需的。
Zotero 插件