Research ArticleBIOPHYSICS

Molecular recognition of human islet amyloid polypeptide assembly by selective oligomerization of thioflavin T

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Science Advances  05 Aug 2020:
Vol. 6, no. 32, eabc1449
DOI: 10.1126/sciadv.abc1449
  • Fig. 1 Self-assembly of hIAPP8–37 at HOPG surfaces.

    (A) Primary sequence of hIAPP8–37. (B) A representative STM image of the hIAPP8–37 self-assembly on the HOPG surface. Tunneling condition: I = 299.1 pA and V = 529.8 mV. The molecular axes of the hIAPP8–37 peptide strands are indicated by the yellow double-headed arrow. The inset in (B) shows a statistical histogram of the d between the two adjacent peptide strands.

  • Fig. 2 Adsorption of ThT on hIAPP8–37 monolayer self-assembly.

    (A) Perpendicular (left) and planar (right) resonance forms of ThT with the torsion angle φ between the benzothiazole and the benzylamine moieties. The blue and green planes represent the planes of the benzothiazole and the benzylamine moieties, respectively. The torsion angle φ is the dihedral angle between these two planes. (B) Representative STM image of hIAPP8–37/ThT coassembly on the surface of HOPG. Tunneling condition: I = 299.1 pA and V = 589.0 mV. Cross-sectional profiles corresponding to the white line in (B). The blue and yellow triangles label the peak and the valley, respectively.

  • Fig. 3 Coassembly of hIAPP8–37/4Bpy at HOPG surfaces.

    (A) Molecular structure of 4Bpy. (B) Representative STM image of the coassembly of hIAPP8–37/4Bpy at HOPG surfaces. Tunneling condition: I = 299.1 pA and V = 539.2 mV. The yellow and white lines depict the molecular axis of the hIAPP8–37 strand and the string composed of 4Bpy molecules, respectively. Inset in (B) shows the distribution of L of hIAPP8–37 and the proposed structure of the coassembly of hIAPP8–37/4Bpy. AAs, amino acids.

  • Fig. 4 Selective oligomerization of ThT atop hIAPP8–37 with 4Bpy.

    (A to D) Representative STM image of ThT adsorption at hIAPP8–37/4Bpy surfaces. Tunneling conditions: I = 299.1 pA and V = 519.4 mV. Inset in (A) represents the cross-sectional profile corresponding to the white line. The blue and yellow triangles label the peak and the valley in (A). (E) STM contrast of ThT in the absence (gray) or presence (green) of 4Bpy. (F and G) Scheme and STM images of ThT oligomers before (left) (G) and after (right) (G) removal of ThT molecules. The dashed circle highlights the part removed by the STM tip.

  • Fig. 5 Oligomerization states of ThT on hIAPP8–37.

    (A) Measured and simulated oligomerization states of ThT on hIAPP8–37/4Bpy coassembly surfaces. (B and C) Number distribution of different types of ThT oligomers determined by (B) the number of oligomers and (C) the number of constituent ThT units. (D) Relative energy difference between 1 × 2, 2 × 1, and 2 × 2 oligomerization states. (E and F) Schematic illustration of (E) cohesive interactions within a 2 × 2 ThT tetramer and (F) adhesive interactions between a ThT monomer and protein substrate. Color codes for (E) and (F): green for carbon, yellow for sulfur, blue for nitrogen, white for hydrogen, and gray for hIAPP8–37. (G) A schematic illustration of relative energy difference between the 2 × 2, 1 × 4, and 4 × 1 states.

Supplementary Materials

  • Supplementary Materials

    Molecular recognition of human islet amyloid polypeptide assembly by selective oligomerization of thioflavin T

    Lanlan Yu, Wenbo Zhang, Wendi Luo, Robert L. Dupont, Yang Xu, Yibing Wang, Bin Tu, Haiyan Xu, Xiaoguang Wang, Qiaojun Fang, Yanlian Yang, Chen Wang, Chenxuan Wang

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    • Section S1
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