Computer-designed protein targets immune receptor linked to inflammation at new 'undruggable' site

AI Summary

Researchers used computer-designed proteins to target a previously difficult-to-drug site on Toll-like receptor 4 (TLR4), an immune receptor involved in inflammation and infection response. The approach may offer a path toward therapies for conditions associated with excessive TLR4 activity, including sepsis, arthritis, and inflammatory bowel disease; no FDA-approved drugs specifically block the receptor.

To sense their environment and respond accordingly, cells enlist membrane proteins as communication hubs, receiving molecular messages from outside and triggering responses inside. One of these proteins is Toll-like receptor 4 (TLR4), an immune receptor that plays an essential role in protecting against infections. But overactivity of TLR4 has been linked to inflammatory disorders like sepsis, arthritis and inflammatory bowel disease, making it an attractive target for therapies. Despite its appeal, TLR4 is difficult to manipulate precisely, and no FDA-approved drugs specifically block it.