Fig. 4
Molecular mechanism of APP recognition of irisin. a The APP672–699 binding mode on irisin predicted by computational simulations combined to experimental information. The mean of four APP672–699 structures assigned to the top-ranked binding mode was shown. The irisin dimer is represented by the electrostatic surface model, where electropositive, electronegative, and hydrophobic regions are colored by blue, red, and white, respectively. APP672–699 is represented by ribbon and stick models (green for residues 672–687 / yellow for residues 688–699, carbon; blue, nitrogen; red, oxygen). b Superimposition of the predicted irisin-the APP672–699 complex structure and that of the transmembrane domain (residues 683–728) of APP (PDBID:2LP1). Irisin and APP are represented by surface and sphere models, respectively. The putative functional loop regions in irisin (residues 30–32, 55–58, and 106–108) are colored by magenta, and residues 672–687 and 688–728 in APP are colored by yellow and green, respectively. The extracellular and intracellular membrane surfaces predicted by Orientations of Proteins in Membranes (OPM) database (ref) are depicted by red and blue dots, respectively