New Structure of LAG-3

New Structure of LAG-3 Researchers co-crystallized the LAG-3 D1-D4 domains with a single-chain variable fragment (scFv) of an F7 antagonist to characterize the structure of the LAG-3 extracellular domain. It was found that LAG-3 is formed as a homodimer through the D2 structural domain, with the remaining structural domains forming an elongated and curved arrangement. the dimer interface in D2 is at an angle, so that the D1 structural domain deviates from the central axis of the dimer and forms a V-shaped aperture. The dimerization interfaces in human and mouse LAG-3 structures share a broadly conserved set of residues, but the angles of D1D2 dimer formation are extremely different. This may result in different relative positions of the MHCII and FGL1 binding sites. This conformational difference between human and mouse LAG-3 may reflect two distinct functional states of LAG-3. In addition to resolving structural information on the extracellular structural domain of LAG-3, key interfacial residues in the LAG-3 D1 loop 2 were identified and it was demonstrated that LAG-3 binds MHCII and FGL1 via different molecular surfaces.