Disordered flanks prevent peptide aggregation.

Natively unstructured or disordered regions appear to be abundant in eukaryotic proteins. Many such regions have been found alongside small linear binding motifs. We report a Monte Carlo study that aims to elucidate the role of disordered regions adjacent to such binding motifs. The coarse-grained s...

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Autores principales:	Sanne Abeln, Daan Frenkel
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/b329eb55103644ce8989b2e9a27c9e01
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spelling	oai:doaj.org-article:b329eb55103644ce8989b2e9a27c9e012021-11-25T05:41:56ZDisordered flanks prevent peptide aggregation.1553-734X1553-735810.1371/journal.pcbi.1000241https://doaj.org/article/b329eb55103644ce8989b2e9a27c9e012008-12-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19096500/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Natively unstructured or disordered regions appear to be abundant in eukaryotic proteins. Many such regions have been found alongside small linear binding motifs. We report a Monte Carlo study that aims to elucidate the role of disordered regions adjacent to such binding motifs. The coarse-grained simulations show that small hydrophobic peptides without disordered flanks tend to aggregate under conditions where peptides embedded in unstructured peptide sequences are stable as monomers or as part of small micelle-like clusters. Surprisingly, the binding free energy of the motif is barely decreased by the presence of disordered flanking regions, although it is sensitive to the loss of entropy of the motif itself upon binding. This latter effect allows for reversible binding of the signalling motif to the substrate. The work provides insights into a mechanism that prevents the aggregation of signalling peptides, distinct from the general mechanism of protein folding, and provides a testable hypothesis to explain the abundance of disordered regions in proteins.Sanne AbelnDaan FrenkelPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 4, Iss 12, p e1000241 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Sanne Abeln Daan Frenkel Disordered flanks prevent peptide aggregation.
description	Natively unstructured or disordered regions appear to be abundant in eukaryotic proteins. Many such regions have been found alongside small linear binding motifs. We report a Monte Carlo study that aims to elucidate the role of disordered regions adjacent to such binding motifs. The coarse-grained simulations show that small hydrophobic peptides without disordered flanks tend to aggregate under conditions where peptides embedded in unstructured peptide sequences are stable as monomers or as part of small micelle-like clusters. Surprisingly, the binding free energy of the motif is barely decreased by the presence of disordered flanking regions, although it is sensitive to the loss of entropy of the motif itself upon binding. This latter effect allows for reversible binding of the signalling motif to the substrate. The work provides insights into a mechanism that prevents the aggregation of signalling peptides, distinct from the general mechanism of protein folding, and provides a testable hypothesis to explain the abundance of disordered regions in proteins.
format	article
author	Sanne Abeln Daan Frenkel
author_facet	Sanne Abeln Daan Frenkel
author_sort	Sanne Abeln
title	Disordered flanks prevent peptide aggregation.
title_short	Disordered flanks prevent peptide aggregation.
title_full	Disordered flanks prevent peptide aggregation.
title_fullStr	Disordered flanks prevent peptide aggregation.
title_full_unstemmed	Disordered flanks prevent peptide aggregation.
title_sort	disordered flanks prevent peptide aggregation.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/b329eb55103644ce8989b2e9a27c9e01
work_keys_str_mv	AT sanneabeln disorderedflankspreventpeptideaggregation AT daanfrenkel disorderedflankspreventpeptideaggregation
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Disordered flanks prevent peptide aggregation.

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