The Route from the Folded to the Amyloid State: Exploring the Potential Energy Surface of a Drug‐Like Miniprotein

Taricska, Nóra; Horváth, Dániel; Menyhárd, Dóra K.; Ákontz-Kiss, Hanna; Noji, Masahiro; So, Masatomo; Goto, Yuji; Fujiwara, Toshimichi; Perczel, András

doi:10.1002/chem.201905181

Chemistry A European J

2020

DOI: 10.1002/chem.201905181

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The Route from the Folded to the Amyloid State: Exploring the Potential Energy Surface of a Drug‐Like Miniprotein

Nóra Taricska

Dániel Horváth

Dóra K. Menyhárd

et al.

Abstract: Invited for the cover of this issue is the group of András Perczel at Eötvös Loránd University, Budapest, Hungary and colleagues from Osaka University, Japan. The image depicts the amyloid buildup of an Exenatide derivate miniprotein (E5) monitored on a simplified hyperspace. Read the full text of the article at 10.1002/chem.201903826.

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Solvent induced amyloid polymorphism and the uncovering of the elusive class 3 amyloid topology

Dürvanger,

Bencs,

Menyhárd

et al. 2024

Commun Biol

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Aggregation-prone-motifs (APRs) of proteins are short segments, which – as isolated peptides - form diverse amyloid-like crystals. We introduce two APRs - designed variants of the incretin mimetic Exendin-4 - that both display crystal-phase polymorphism. Crystallographic and spectroscopic analysis revealed that a single amino-acid substitution can greatly reduce topological variability: while LYIQWL can form both parallel and anti-parallel β-sheets, LYIQNL selects only the former. We also found that the parallel/anti-parallel switch of LYIQWL can be induced by simply changing the crystallization temperature. One crystal form of LYIQNL was found to belong to the class 3 topology, an arrangement previously not encountered among proteinogenic systems. We also show that subtle environmental changes lead to crystalline assemblies with different topologies, but similar interfaces. Spectroscopic measurements showed that polymorphism is already apparent in the solution state. Our results suggest that the temperature-, sequence- and environmental sensitivity of physiological amyloids is reflected in assemblies of the APR segments, which, complete with the new class 3 crystal form, effectively sample all the originally proposed basic topologies of amyloid-like aggregates.

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Solvent induced amyloid polymorphism and the uncovering of the elusive class 3 amyloid topology

Dürvanger,

Bencs,

Menyhárd

et al. 2024

Commun Biol

View full text Add to dashboard Cite

show abstract

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The Route from the Folded to the Amyloid State: Exploring the Potential Energy Surface of a Drug‐Like Miniprotein

Cited by 1 publication

References 54 publications

Solvent induced amyloid polymorphism and the uncovering of the elusive class 3 amyloid topology

Solvent induced amyloid polymorphism and the uncovering of the elusive class 3 amyloid topology

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