Overcoming the LAG3 phase problem

Abstract

Lymphocyte activation gene 3 (LAG3) is an important checkpoint inhibitor molecule of immunotherapeutic interest. New crystal structures of LAG3 provide important insight into its molecular architecture, laying the groundwork for future basic and applied investigations.

Fig. 1. LAG3 structure, flexibility and comparison to co-stimulatory molecules and co-receptors.

a, Comparison of the crystal structures of mouse LAG3 dimer including domains D1 and D2 (left), and human LAG3 dimer including domains D1–D4 (right) from the LAG3 complex structure with F7 scFv (not shown). Protein surface representations are coloured according to observed positional variability of domains (D1, D2 and D3D4), with arrows indicating presumed inter-domain flexibility of human LAG3 D1D4. b, Structures of T cell co-stimulatory molecules PD1, CTLA4, LAG3 and CD4 shown as tube representations. Figure created with BioRender.com.