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Author Notes:

David G. Lynn, dlynn2@emory.edu

Initial project design and implementation: AR and DL; Initial experiments: AR, RC, and JS-C; Completing experiments: CG-K, GP, AB, RL, and ABR; Figure preparation: AR and CG-K; Data interpretation and analysis: CG-K, AR, GP, and DL; Manuscript drafting: CG-K, GP, AR, JS-C, and DL.

We also thank Bing Wang and Shaoxiong Wu from the Emory NMR Center for NMR assistance, Fred Strobel for mass spectrometry analysis, and Gonen Ashkenasy for advice and suggestions.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Subject:

Research Funding:

The research was supported primarily by NSF DMR-2004846 BMAT in collaboration with BSF 2019745 with early resource access from NIH Alzheimer’s Disease Research Center P50AG025688. This study was supported by the Robert P. Apkarian Integrated Electron Microscopy Core (IEMC) at Emory University, which is subsidized by the School of Medicine and Emory College of Arts and Sciences. Additional support was provided by the Georgia Clinical and Translational Science Alliance of the National Institutes of Health under award number UL1TR000454. The content is solely the responsibility of the authors and does not necessarily reflect the official views of the National Institutes of Health.

Polyanion order controls liquid-to-solid phase transition in peptide/nucleic acid co-assembly

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Journal Title:

Frontiers in Molecular Biosciences

Volume:

Volume 9

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Type of Work:

Article | Final Publisher PDF

Abstract:

The Central Dogma highlights the mutualistic functions of protein and nucleic acid biopolymers, and this synergy appears prominently in the membraneless organelles widely distributed throughout prokaryotic and eukaryotic organisms alike. Ribonucleoprotein granules (RNPs), which are complex coacervates of RNA with proteins, are a prime example of these membranelles organelles and underly multiple essential cellular functions. Inspired by the highly dynamic character of these organelles and the recent studies that ATP both inhibits and templates phase separation of the fused in sarcoma (FUS) protein implicated in several neurodegenerative diseases, we explored the RNA templated ordering of a single motif of the Aβ peptide of Alzheimer’s disease. We now know that this strong cross-β propensity motif alone assembles through a liquid-like coacervate phase that can be externally templated to form distinct supramolecular assemblies. Now we provide evidence that structured phosphates, ranging from complex structures like double stranded and quadraplex DNA to simple trimetaphosphate, differentially impact the liquid to solid phase transition necessary for paracrystalline assembly. The results from this simple model illustrate the potential of ordered environmental templates in the transition to potentially irreversible pathogenic assemblies and provides insight into the ordering dynamics necessary for creating functional synthetic polymer co-assemblies.

Copyright information:

© 2022 Gordon-Kim, Rha, Poppitz, Smith-Carpenter, Luu, Roberson, Conklin, Blake and Lynn.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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