Fig. 4: Dynamics and molecular interactions of human disease associated mutation gp130P498L on the transmembrane IL-6 complex.

Atomistic model of the wildtype human IL-6 complex derived from AlphaFold2 models of IL-6 (coral) residues:47-212 IL-6Rα residues:115-315 (green) and gp130 residues:28-653 (blue) embedded in a lipid bilayer (transparent) containing POPC (grey) and cholesterol (light yellow). Location of gp130 disease-affected residue P498L is shown as a tan circle. Within the transmembrane helix of gp130, E617 (pink), L630 (yellow) and N642 (black) are shown as spheres (a). Histograms show distribution of pairwise Cα carbon distances in Å between gp130 residues E617 (b), L630 (c) and N642 (d), for three independent simulations of wildtype (blue) and P498L variant (orange) complexes. Counts refer to the number of frames of the simulation where the distance between pairs of atoms corresponds to the value indicated on the X axis.