A Monte Carlo Study of the Early Steps of Functional Amyloid Formation

Pengfei Tian, Kresten Lindorff-Larsen, Wouter Boomsma, Mogens Høgh Jensen and Daniel Erik Otzen

PLOS ONE, 2016, vol. 11, issue 1, 1-18

Abstract: In addition to their well-known roles in neurodegenerative diseases and amyloidoses, amyloid structures also assume important functional roles in the cell. Although functional amyloid shares many physiochemical properties with its pathogenic counterpart, it is evolutionarily optimized to avoid cytotoxicity. This makes it an interesting study case for aggregation phenomenon in general. One of the most well-known examples of a functional amyloid, E. coli curli, is an essential component in the formation of bacterial biofilm, and is primarily formed by aggregates of the protein CsgA. Previous studies have shown that the minor sequence variations observed in the five different subrepeats (R1-R5), which comprise the CsgA primary sequence, have a substantial influence on their individual aggregation propensities. Using a recently described diffusion-optimized enhanced sampling approach for Monte Carlo simulations, we here investigate the equilibrium properties of the monomeric and dimeric states of these subrepeats, to probe whether structural properties observed in these early stage oligomers are decisive for the characteristics of the resulting aggregate. We show that the dimerization propensities of these peptides have strong correlations with their propensity for amyloid formation, and provide structural insights into the inter- and intramolecular contacts that appear to be essential in this process.

Date: 2016
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0146096 (text/html)
https://journals.plos.org/plosone/article/file?id= ... 46096&type=printable (application/pdf)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0146096

DOI: 10.1371/journal.pone.0146096

Access Statistics for this article

More articles in PLOS ONE from Public Library of Science
Bibliographic data for series maintained by plosone ().