Structure-guided engineering of tick evasins for targeting chemokines in inflammatory diseases

Abstract

Significance Inflammatory diseases collectively account for numerous deaths and morbidity worldwide. New treatment approaches are needed. A central feature of inflammatory diseases is the recruitment of leukocytes to the affected tissues, which is stimulated by secreted proteins called chemokines. Effective suppression of leukocyte recruitment could be achieved by simultaneously targeting multiple chemokines, a natural molecular strategy used by tick salivary proteins called evasins. Here, we describe the structural and molecular features of a tick evasin that control its ability to bind and block a limited set of chemokines. By modifying these features, we demonstrate that evasins can be engineered to alter the array of chemokines that they target. Thus, this study establishes a structure-based paradigm for the development of antiinflammatory therapeutics.