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Amyloid Folding: an Origami-Based Approach

Lima, L. M. T.

2025-06-17 biophysics
10.1101/2025.06.12.659339 bioRxiv
Show abstract

Amyloid is an ordered folding pattern that involves a cross-beta arrangement, with hydrogen-bonding between adjacent chains in the fiber elongation axis, and side-chain interactions perpendicular to it, forming steric and/or polar zippers intra- and/or inter-chains. The arrangement of the polypeptide backbone and the side-chain interactions can be arranged with different morphologies that are repeated along the fiber growth axis as stacking units. A simple representation of amyloid folding of proteins using paper origami is reported here, which can be used to visualize the {beta}-sheet along fiber axis and the perpendicular variability in topological arrangement. The model uses regular office paper, in the form of multiple linearized polypeptide chains, arranged in parallel or anti-parallel forms, connected by hydrogen bonds. Alternating mountain/valley creases along the growth axis of the fibrils and, over the front/back side-chains, results in a pleated sheet that can be used to study the topological arrangement of amyloid fibrils and the polar/steric zippers. The present models can be used as teaching tools for understanding the structural and molecular basis of amyloid folding, chain growth, homo- and cross-seeding, and other features of amyloid function in health, disease and biotechnology. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=117 SRC="FIGDIR/small/659339v1_ufig1.gif" ALT="Figure 1"> View larger version (48K): org.highwire.dtl.DTLVardef@888d0eorg.highwire.dtl.DTLVardef@e4b027org.highwire.dtl.DTLVardef@1e8ff0forg.highwire.dtl.DTLVardef@1c160ed_HPS_FORMAT_FIGEXP M_FIG C_FIG Key featuresO_LIIntroduces a physical origami model of amyloid {beta}-sheet structure using paper folding. C_LIO_LIDemonstrates how hydrogen bonding and side-chain interactions can be conceptualized in 3D. C_LIO_LIModels morphological polymorphism and parallel/antiparallel alignment. C_LIO_LIUseful for teaching complex biophysical concepts like cross-seeding, fibril growth, and molecular stability in amyloids. C_LIO_LIHighlights the educational value for biochemistry, structural biology, biomedical and material sciences. C_LI

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