Electrostatic Complementarity Drives Amyloid/Nucleic Acid Co-assembly

• Type of Material: Article
• Authors: Allisandra K. Rha, Emory University; Dibyendu Das, Emory University; Olga Taran, Emory University; Yonggang Ke, Emory University; Anil K. Mehta, Emory University; David G. Lynn, Emory University
• Language: English
• Date: 2019-11-14
• Publisher: John Wiley and Sons
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2020 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim
• Final Published Version (URL): https://doi.org/10.1002/anie.201907661
• Title of Journal or Parent Work: Angewandte Chemie International Edition
• Volume: 59
• Issue: 1
• Start Page: 358
• End Page: 363
• Grant/Funding Agency: NSF; NIH
• Grant/Funding Information: The research was supported by grants from NSF CHE-1507932 and NSF/DMR-BSF 1610377, and NIH Alzheimer’s Disease Research Center: P50AG025688.
• Keywords: solid-state NMR; Alzheimer’s disease; biopolymer co-assembly; nucleic acid/amyloid co-assembly structure
• Subject - Topics: Molecular biology; Biophysics; Structural biology

Abstract

Proteinaceous plaques associated with neurodegenerative diseases contain many biopolymers including the polyanions glycosaminoglycans and nucleic acids. Polyanion-induced amyloid fibrillation has been implicated in disease etiology, but structural models for amyloid/nucleic acid co-assemblies remain limited. Here we constrain nucleic acid/peptide interactions with model peptides that exploit electrostatic complementarity and define a novel amyloid/nucleic acid co-assembly. The structure provides a model for nucleic acid/amyloid co-assembly as well as insight into the energetic determinants involved in templating amyloid assembly.