Fig. 3: Crystal structure of DLK1 EGF5-6 bound to ACVR2B.
From: Molecular mechanism of Activin receptor inhibition by DLK1
A Crystal structure of DLK1 domains EGF5-6 (magenta) in complex with the extracellular domain of ACVR2B (teal). B A surface model of ACVR2B (teal) with DLK1(magenta) overlaid with a cartoon representation of myostatin (yellow). C Zoom in panel showing Trp78 and Phe101 of ACVR2B forming hydrophobic interactions with Arg193 of DLK1. D Zoom in panel showing Phe82 of ACVR2B packing against Val209 and Val229 of DLK1, and Arg56 of ACVR2B forming a hydrogen bond with Gln228. E SPR isotherms comparing the binding between DLK1(EGF5-6) or DLK1(EGF5-6)R193D-mutant to ACVR2B-Fc. The DLK1 proteins were injected over a sensor chip containing immobilized ACVR2B-Fc and the data was fitted to a 1:1 binding model. RU = resonance units. F SPR isotherms comparing the binding between DLK1 and three ACVR2B-Fc interface mutants. The R56A mutation in ACVR2B was associated with a ~ 6-fold decrease in DLK1-binding affinity compared to WT ACVR2B, and there was a complete loss of DLK1 binding to the W78A or F101A mutants. RU = resonance units. Source data are provided as a Source Data file.
