Fig. 2: The cryo-EM structure of antibody-bound NPR1 suggests that REGN5381 is an allosteric activator.

a, The extracellular domains of an inactive ANP-free NPR1 dimer (PDB: 1DP4) are shown in two different orientations as a molecular surface, one monomer in white and the other monomer in dark grey, with the principal axes of each monomer indicated as thick solid white or grey lines, respectively; the projection angle between the axes is indicated below the monomers. The active, ANP-bound NPR1 dimer (PDB: 1T34) is shown similarly to the diagram at left, as a blue surface for bound ANP. The same complexes are shown in schematic form (extracellular domain, transmembrane helix, ANP) on the right, including possible positions for the transmembrane helices. b, The NPR1–ANP–REGN5381 complex is shown similarly to a. c, The NPR1–REGN5381 complex is shown similarly to a, with the addition of REGN5381 Fab molecular surface in red.