Extended Data Fig. 3: The fuzzy coat in hIAPP fibril structure may represent the flexible N-terminal of hIAPP and the SUMO-tag. | Nature Structural & Molecular Biology

Extended Data Fig. 3: The fuzzy coat in hIAPP fibril structure may represent the flexible N-terminal of hIAPP and the SUMO-tag.

From: Cryo-EM structure and inhibitor design of human IAPP (amylin) fibrils

Extended Data Fig. 3

a, The final reconstruction (left) and 2D classification (right) show a fuzzy coat of ~55 Å surrounding the fibril core. b, Protease cleavage assays indicate the construct we used for fibril structure determination (SUMO-IAPP with 1xG, means one glycine between SUMO-tag and hIAPP) has an un-removable SUMO-tag, whereas the SUMO-tag is removable when we extend the linker to three glycine. c, Plausible N-terminal conformation suggested by the extra densities near Asn14. The density map with σ=3.0 is shown in blue mesh and that with σ=2.0 is shown in grey mesh. The intra-molecular disulfide bond is labeled between Cys2 and Cys7, and the residues occupying the extra densities in our hypothetical model are underlined. d, Crystal structure of SUMO protein (PDB ID 1L2N). e, Hypothetical model of N-terminus of hIAPP and SUMO-tag match the dimensions of the fuzzy coat observed in the hIAPP fibril reconstruction. Notice that in most cases the SUMO-tag is far away from the fibril core therefore should not influence the fibril structure.

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