A Requirement for Metamorphic Interconversion in the Antimicrobial Activity of Chemokine XCL1

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• 作者：Amanda M. Nevins ; Akshay Subramanian ; Jazma L. Tapia ; David P. Delgado ; Robert C. Tyler ; Davin R. Jensen ; André J. Ouellette ; Brian F. Volkman
• 刊名：Biochemistry
• 出版年：2016
• 出版时间：July 12, 2016
• 年：2016
• 卷：55
• 期：27
• 页码：3784-3793
• 全文大小：609K
• 年卷期：0
• ISSN：1520-4995

文摘

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.