Fig. 3: Structural basis for leptin-dependent LepR dimerization.
From: Structural insights into the mechanism of leptin receptor activation
a Front view of the segmented density map of the leptin-LepRD3-D7 complex resolved to 4.5 Å resolution (transparent) with the focus refined map encompassing leptin and the leptin-binding domains of LepR, resolved to 3.8 Å resolution (solid). b, c Close-up views of the leptin-LepR site 2 binding interface. Hydrogen bonds and salt-bridges are shown as black dashed-lines. d Immunoblot of lysates prepared from HEK-293T cells transiently expressing the indicated LepR constructs and stimulated with the indicated concentration of recombinant leptin for 20 min. Representative result of experiment performed two times. e Top view of the segmented density maps shown in (a). f Close-up view of the leptin-LepR site 3a binding interface. g Immunoblot of lysates prepared and analyzed as in (c). Representative result of experiment performed two times. h Comparison of the apo-leptin structure (PDB ID: 1AX8) and LepR-bound leptin structure (this paper, PDB ID: 8DHA), showing leptin in salmon, LepR D3 in purple. i Close-up view of the leptin-LepR site 3b binding interface. j LepR-dependent ordering of the leptin AB loop residues 24–39, shown in green. k Immunoblot of lysates prepared from HEK-293T cells stably expressing wild-type LepR and stimulated with the indicated leptin variants for 20 min. Representative result of experiment performed three times.
