Specific activation of the TLR1-TLR2 heterodimer by small-molecule agonists.

Toll-like receptor (TLR) agonists activate both the innate and the adaptive immune systems. These TLR agonists have been exploited as potent vaccine adjuvants and antitumor agents. We describe the identification and characterization of a small molecule, -methyl-4-nitro-2-(4-(4-(trifluoromethyl)phenyl)-1 -imidazol-1-yl)aniline (CU-T12-9), that directly targets TLR1/2 to initiate downstream signaling.

A lysine-rich motif in the phosphatidylserine receptor PSR-1 mediates recognition and removal of apoptotic cells.

The conserved phosphatidylserine receptor (PSR) was first identified as a receptor for phosphatidylserine, an 'eat-me' signal exposed by apoptotic cells. However, several studies suggest that PSR may also act as an arginine demethylase, a lysyl hydroxylase, or an RNA-binding protein through its N-terminal JmjC domain. How PSR might execute drastically different biochemical activities, and whether they are physiologically significant, remain unclear.

Isolated Toll-like receptor transmembrane domains are capable of oligomerization.

Toll-like receptors (TLRs) act as the first line of defense against bacterial and viral pathogens by initiating critical defense signals upon dimer activation. The contribution of the transmembrane domain in the dimerization and signaling process has heretofore been overlooked in favor of the extracellular and intracellular domains. As mounting evidence suggests that the transmembrane domain is a critical region in several protein families, we hypothesized that this was also the case for Toll-like receptors.