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. Author manuscript; available in PMC: 2022 Oct 1.
Published in final edited form as: Nat Struct Mol Biol. 2022 Mar 31;29(4):357–368. doi: 10.1038/s41594-022-00750-6

Figure 6. Structures of IR/insulin WT complex at subsaturated insulin concentrations.

Figure 6.

a. 3D reconstruction of the IR/insulin WT in two insulins bound, symmetric conformation, and the corresponding ribbon representation fitted into cryo-EM map at 3.5 Å resolution. The symmetric cryo-EM structure was reconstructed from 21.5% of good particles.

b. 3D reconstruction of the IR/insulin WT in a single insulin bound, asymmetric conformation, and the corresponding ribbon representation fitted into cryo-EM map at 4.9 Å resolution, shown in three orthogonal views. The asymmetric cryo-EM structure was reconstructed from 9.5% of well-defined asymmetric particles.

c. 3D reconstruction of the IR/insulin WT in two insulins bound, asymmetric conformation, and the corresponding ribbon representation fitted into cryo-EM map at 4.4 Å resolution. The asymmetric cryo-EM structure was reconstructed from 19.3% of well-defined asymmetric particles. The ribbon representation of the asymmetric IR/insulin WT complex, shown in two orthogonal views. The top view of the asymmetric IR/insulin WT complex, showing, in half of the complex, one insulin bound at site-1 of one protomer also weakly contacts the side-surface of FnIII-1 domain of another protomer. The cryo-EM densities of insulins are shown.

d. 3D reconstruction of the IR/insulin WT in two insulins bound, asymmetric conformation, and the corresponding ribbon representation fitted into cryo-EM map at 4 Å resolution. The asymmetric cryo-EM structure was reconstructed from 71.2% of well-defined asymmetric particles. The ribbon representation of the asymmetric IR/insulin WT complex, shown in two orthogonal views. The top view of the asymmetric IR/insulin WT complex, showing, in half of the complex, one insulin bound at site-2 of one protomer also weakly contacts the site 1a of neighboring protomer. The cryo-EM densities of insulins are shown.

e. Cryo-EM density and model of dimerized α-CT motifs in a single insulin bound, asymmetric IR (b).

f. Cryo-EM density and model of dimerized α-CT motifs in two insulins bound, asymmetric IR (d).