Fig. 5: Peptide screening of variant cross-interactions with the VQIVYK aggregation-prone region from tau. | Nature Communications

Fig. 5: Peptide screening of variant cross-interactions with the VQIVYK aggregation-prone region from tau.

From: Mapping the sequence specificity of heterotypic amyloid interactions enables the identification of aggregation modifiers

Fig. 5

Th-T kinetic assays of VQIVYK-alone (125 μM) or in the sub-stoichiometric presence of the strongest a co-aggregating or b inhibiting single-position variants (25 μM). Curves are shown as means ± SD (n = 3 biologically independent samples). c Volcano plot analysis of the kinetic halftimes for the entire peptide screen (Fig. S4). Green- and blue-shaded backgrounds indicate capping and co-aggregating sequences of high significance. Sequences with a strong thermodynamic profile for capping or heterotypic interaction are shown in green or purple points, respectively, whereas mutants of the Ile residue are shown in yellow. Statistical significance was determined using one-way ANOVA with Tukey’s test for multiple comparisons (compared to VQIVYK-alone halftime). d, e End-state fluorescence (n = 3 biologically independent samples) and f, g critical concentration (n = 4 biologically independent samples) modifications induced by the strongest d–f heterotypic aggregating and e–g capping sequences. Statistical significance was determined using one-way ANOVA with Tukey’s test for multiple comparisons (compared to VQIVYK-alone). h Electron micrographs (n = 3 independent repeats) of capping mix samples after 7 days of incubation. Minimal to no fibril formation was observed for the strongest cappers (V1W, K6P, V1Y, V1F). Source data are provided as a Source Data file.

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