Intermolecular β-strand networks avoid hub residues and favor low interconnectedness: a potential protection mechanism against chain dissociation upon mutation.

Altogether few protein oligomers undergo a conformational transition to a state that impairs their function and leads to diseases. But when it happens, the consequences are not harmless and the so-called conformational diseases pose serious public health problems. Notorious examples are the Alzheime...

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Autores principales: Giovanni Feverati, Mounia Achoch, Laurent Vuillon, Claire Lesieur
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Publicado: Public Library of Science (PLoS) 2014
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spelling oai:doaj.org-article:ed00533eff3f48c4b88310fc8745b6462021-11-18T08:23:22ZIntermolecular β-strand networks avoid hub residues and favor low interconnectedness: a potential protection mechanism against chain dissociation upon mutation.1932-620310.1371/journal.pone.0094745https://doaj.org/article/ed00533eff3f48c4b88310fc8745b6462014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24733378/?tool=EBIhttps://doaj.org/toc/1932-6203Altogether few protein oligomers undergo a conformational transition to a state that impairs their function and leads to diseases. But when it happens, the consequences are not harmless and the so-called conformational diseases pose serious public health problems. Notorious examples are the Alzheimer's disease and some cancers associated with a conformational change of the amyloid precursor protein (APP) and of the p53 tumor suppressor, respectively. The transition is linked with the propensity of β-strands to aggregate into amyloid fibers. Nevertheless, a huge number of protein oligomers associate chains via β-strand interactions (intermolecular β-strand interface) without ever evolving into fibers. We analyzed the layout of 1048 intermolecular β-strand interfaces looking for features that could provide the β-strands resistance to conformational transitions. The interfaces were reconstructed as networks with the residues as the nodes and the interactions between residues as the links. The networks followed an exponential decay degree distribution, implying an absence of hubs and nodes with few links. Such layout provides robustness to changes. Few links per nodes do not restrict the choices of amino acids capable of making an interface and maintain high sequence plasticity. Few links reduce the "bonding" cost of making an interface. Finally, few links moderate the vulnerability to amino acid mutation because it entails limited communication between the nodes. This confines the effects of a mutation to few residues instead of propagating them to many residues via hubs. We propose that intermolecular β-strand interfaces are organized in networks that tolerate amino acid mutation to avoid chain dissociation, the first step towards fiber formation. This is tested by looking at the intermolecular β-strand network of the p53 tetramer.Giovanni FeveratiMounia AchochLaurent VuillonClaire LesieurPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 4, p e94745 (2014)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Giovanni Feverati
Mounia Achoch
Laurent Vuillon
Claire Lesieur
Intermolecular β-strand networks avoid hub residues and favor low interconnectedness: a potential protection mechanism against chain dissociation upon mutation.
description Altogether few protein oligomers undergo a conformational transition to a state that impairs their function and leads to diseases. But when it happens, the consequences are not harmless and the so-called conformational diseases pose serious public health problems. Notorious examples are the Alzheimer's disease and some cancers associated with a conformational change of the amyloid precursor protein (APP) and of the p53 tumor suppressor, respectively. The transition is linked with the propensity of β-strands to aggregate into amyloid fibers. Nevertheless, a huge number of protein oligomers associate chains via β-strand interactions (intermolecular β-strand interface) without ever evolving into fibers. We analyzed the layout of 1048 intermolecular β-strand interfaces looking for features that could provide the β-strands resistance to conformational transitions. The interfaces were reconstructed as networks with the residues as the nodes and the interactions between residues as the links. The networks followed an exponential decay degree distribution, implying an absence of hubs and nodes with few links. Such layout provides robustness to changes. Few links per nodes do not restrict the choices of amino acids capable of making an interface and maintain high sequence plasticity. Few links reduce the "bonding" cost of making an interface. Finally, few links moderate the vulnerability to amino acid mutation because it entails limited communication between the nodes. This confines the effects of a mutation to few residues instead of propagating them to many residues via hubs. We propose that intermolecular β-strand interfaces are organized in networks that tolerate amino acid mutation to avoid chain dissociation, the first step towards fiber formation. This is tested by looking at the intermolecular β-strand network of the p53 tetramer.
format article
author Giovanni Feverati
Mounia Achoch
Laurent Vuillon
Claire Lesieur
author_facet Giovanni Feverati
Mounia Achoch
Laurent Vuillon
Claire Lesieur
author_sort Giovanni Feverati
title Intermolecular β-strand networks avoid hub residues and favor low interconnectedness: a potential protection mechanism against chain dissociation upon mutation.
title_short Intermolecular β-strand networks avoid hub residues and favor low interconnectedness: a potential protection mechanism against chain dissociation upon mutation.
title_full Intermolecular β-strand networks avoid hub residues and favor low interconnectedness: a potential protection mechanism against chain dissociation upon mutation.
title_fullStr Intermolecular β-strand networks avoid hub residues and favor low interconnectedness: a potential protection mechanism against chain dissociation upon mutation.
title_full_unstemmed Intermolecular β-strand networks avoid hub residues and favor low interconnectedness: a potential protection mechanism against chain dissociation upon mutation.
title_sort intermolecular β-strand networks avoid hub residues and favor low interconnectedness: a potential protection mechanism against chain dissociation upon mutation.
publisher Public Library of Science (PLoS)
publishDate 2014
url https://doaj.org/article/ed00533eff3f48c4b88310fc8745b646
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AT mouniaachoch intermolecularbstrandnetworksavoidhubresiduesandfavorlowinterconnectednessapotentialprotectionmechanismagainstchaindissociationuponmutation
AT laurentvuillon intermolecularbstrandnetworksavoidhubresiduesandfavorlowinterconnectednessapotentialprotectionmechanismagainstchaindissociationuponmutation
AT clairelesieur intermolecularbstrandnetworksavoidhubresiduesandfavorlowinterconnectednessapotentialprotectionmechanismagainstchaindissociationuponmutation
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