Crystal structure of the C‐terminal domain of mouse TLR9

Toll‐like receptors (TLRs) are important pattern recognition receptors that function in innate immunity. Elucidating the structure and signaling mechanisms of TLR9, a sensor of foreign and endogenous DNA, is essential for understanding its key role in immunity against microbial pathogens as well as in autoimmunity. Abundant evidence suggests that the TLR9‐CTD (C‐terminal domain) by itself is capable of DNA binding and signaling. The crystal structure of unliganded mouse TLR9‐CTD is presented. TLR9‐CTD exhibits one unique feature, a cluster of stacked aromatic and arginine side chains on its concave face. Overall, its structure is most related to the TLR8‐CTD, suggesting a similar mode of ligand binding and signaling. Proteins 2014; 82:2874–2878. © 2014 Wiley Periodicals, Inc.