Inflammation is the body's response to noxious stimuli or conditions, such as infections and injuries. Leukocyte recruitment is a critical process in the inflammatory response mediated by small family of proteins called chemokines. Chemokines are categorized into two main groups, CC and CXC, based on conserved cysteine residues at N-terminus, and they bind promiscuously to chemokine receptors. Numerous species of ticks express two unique families (Class A and Class B) of chemokine-binding proteins (CKBPs) referred to as "evasins" that bind to and inhibit mammalian chemokines, suppressing host inflammation to allow for extended feeding without being detected. Notably, Class A (A1, A2, and A3) evasins bind exclusively to CC chemokines, while Class B evasins target CXC chemokines.
Recently, we have discovered a novel A3 evasin EVA-ATL1001, from the tick Amblyomma tuberculatum containing five disulphide bonds. The A3 evasin EVA-ATL1001 expressed in E. coli binds to multiple CC chemokines with high affinity. Additionally, it binds and inhibits CXC chemokines, though with relatively low affinity and potency. This marks EVA-ATL1001 as the first evasin demonstrated to bind and inhibit both CC and CXC chemokines.The key question posed by the current findings pertains to the mechanism through which EVA-ATL1001 binds to CXC chemokines alongside CC chemokines. Although previous studies have elucidated structures of evasins and their complexes with chemokines, the structural analysis of EVA-ATL1001 in its recognition of both CC and CXC chemokines remains elusive.Understanding the unique interaction of A3 evasin EVA-ATL1001 with chemokines is crucial, as it could pave the way for rational or combinatorial engineering of evasins to target both major classes of chemokines. This innovation is promising for the development of anti-inflammatory therapeutics, particularly for diseases where chemokines play a dominant role in disease progression.