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◇ bioRxiv2026-09-18· biophysics

Charged residues, not aromatics, are the universal topological hubs of intrinsically disordered proteins

T. Rahman, V. N. Uversky

原始摘要(英文原文)· Original abstract
The stickers and spacers model assigns aromatic residues as the primary drivers of IDP phase separation predicting that aromatics also occupy topologically central hub positions in IDP contact networks. Analysing a proteome wide simulation dataset spanning six taxa we find that charged residues not aromatics are the universal network hubs with glutamate the strongest hub in every taxon and aromatics predominantly anti hub. All IDP contact networks are universally positively assortative a sequence encoded topological law in which hub identity is positionally encoded. That hub character requires charge carrier geometry rather than charge alone is demonstrated by a natural experiment in which arginine and lysine carry identical net charge yet arginine is a universal hub while lysine is a near neutral spacer (Cohens d = 2.456) confirmed by force field cross validation and wet lab condensate miscibility data. Charge matched synuclein K[->]R slab simulations reveal that hub character governs condensate density and thermodynamic stability without altering the nucleation threshold connecting single chain topology to multi chain phase thermodynamics. Tyrosine hub character tracks the prokaryote eukaryote boundary with evolutionary encoding the only explanation to survive direct testing. Together these results establish hub identity and sticker identity as complementary organisational principles of disordered sequences governed by distinct residue chemistries and shaped independently by selection.
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Charged residues, not aromatics, are the universal topological hubs of intrinsically disordered proteins — 科研速览 Science Skim