Single-chain and condensed-state behavior of hnRNPA1 from molecular simulations

Publikationstyp:
Zeitschriftenaufsatz
Metadaten:
Autoren
  • D Janka Bauer
  • Lukas S Stelzl
  • Arash Nikoubashman
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000885378200001&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1063/5.0105540
eISSN
1089-7690
Externe Identifier
  • Clarivate Analytics Document Solution ID: 6H3XZ
  • PubMed Identifier: 36272811
ISSN
0021-9606
Ausgabe der Veröffentlichung
15
Zeitschrift
JOURNAL OF CHEMICAL PHYSICS
Artikelnummer
ARTN 154903
Datum der Veröffentlichung
2022
Status
Published
Titel
Single-chain and condensed-state behavior of hnRNPA1 from molecular simulations
Sub types
  • Article
Ausgabe der Zeitschrift
157

Datenquelle: Web of Science (Lite)

Andere Metadatenquellen:
Abstract
<jats:p>Intrinsically disordered proteins (IDPs) are essential components for the formation of membraneless organelles, which play key functional and regulatory roles within biological systems. These complex assemblies form and dissolve spontaneously over time via liquid–liquid phase separation of IDPs. Mutations in their amino acid sequence can alter their phase behavior, which has been linked to the emergence of severe diseases. We study the conformation and phase behavior of a low-complexity domain of heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) using coarse-grained implicit solvent molecular dynamics simulations. We systematically analyze how these properties are affected by the number of aromatic residues within the examined sequences. We find a significant compaction of the chains and an increase in the critical temperature with an increasing number of aromatic residues. The local persistence length is determined in single-chain simulations, revealing strong sequence-specific variations along the chain contour. Comparing single-chain and condensed-state simulations, we find many more collapsed polymer conformations in the dilute systems, even at temperatures near the estimated θ-temperature of the solution. These observations strongly support the hypothesis that aromatic residues play a dominant role in condensation, which is further corroborated by a detailed analysis of the intermolecular contacts, and conversely that important properties of condensates are captured in coarse-grained simulations. Interestingly, we observe density inhomogeneities within the condensates near criticality, which are driven by electrostatic interactions. Finally, we find that the relatively small fraction of hydrophobic residues in the IDPs results in interfacial tensions, which are significantly lower compared to typical combinations of immiscible simple liquids.</jats:p>
Autoren
  • D Janka Bauer
  • Lukas S Stelzl
  • Arash Nikoubashman
DOI
10.1063/5.0105540
eISSN
1089-7690
ISSN
0021-9606
Ausgabe der Veröffentlichung
15
Zeitschrift
The Journal of Chemical Physics
Sprache
en
Online publication date
2022
Datum der Veröffentlichung
2022
Status
Published
Herausgeber
AIP Publishing
Herausgeber URL
http://dx.doi.org/10.1063/5.0105540
Datum der Datenerfassung
2023
Titel
Single-chain and condensed-state behavior of hnRNPA1 from molecular simulations
Ausgabe der Zeitschrift
157

Datenquelle: Crossref

Abstract
Intrinsically disordered proteins (IDPs) are essential components for the formation of membraneless organelles, which play key functional and regulatory roles within biological systems. These complex assemblies form and dissolve spontaneously over time via liquid-liquid phase separation of IDPs. Mutations in their amino acid sequence can alter their phase behavior, which has been linked to the emergence of severe diseases. We study the conformation and phase behavior of a low-complexity domain of heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) using coarse-grained implicit solvent molecular dynamics simulations. We systematically analyze how these properties are affected by the number of aromatic residues within the examined sequences. We find a significant compaction of the chains and an increase in the critical temperature with an increasing number of aromatic residues. The local persistence length is determined in single-chain simulations, revealing strong sequence-specific variations along the chain contour. Comparing single-chain and condensed-state simulations, we find many more collapsed polymer conformations in the dilute systems, even at temperatures near the estimated θ-temperature of the solution. These observations strongly support the hypothesis that aromatic residues play a dominant role in condensation, which is further corroborated by a detailed analysis of the intermolecular contacts, and conversely that important properties of condensates are captured in coarse-grained simulations. Interestingly, we observe density inhomogeneities within the condensates near criticality, which are driven by electrostatic interactions. Finally, we find that the relatively small fraction of hydrophobic residues in the IDPs results in interfacial tensions, which are significantly lower compared to typical combinations of immiscible simple liquids.
Addresses
  • Institute of Physics, Johannes Gutenberg University Mainz, Staudingerweg 7, 55128 Mainz, Germany.
Autoren
  • D Janka Bauer
  • Lukas S Stelzl
  • Arash Nikoubashman
DOI
10.1063/5.0105540
eISSN
1089-7690
Externe Identifier
  • PubMed Identifier: 36272811
Funding acknowledgements
  • Deutsche Forschungsgemeinschaft: 274340645
  • Deutsche Forschungsgemeinschaft: 233630050
  • Deutsche Forschungsgemeinschaft: 405552959
  • Deutsche Forschungsgemeinschaft: 470113688
Open access
false
ISSN
0021-9606
Ausgabe der Veröffentlichung
15
Zeitschrift
The Journal of chemical physics
Schlüsselwörter
  • Polymers
  • Solvents
  • Biochemical Phenomena
  • Intrinsically Disordered Proteins
  • Heterogeneous Nuclear Ribonucleoprotein A1
Sprache
eng
Medium
Print
Paginierung
154903
Datum der Veröffentlichung
2022
Status
Published
Datum der Datenerfassung
2022
Titel
Single-chain and condensed-state behavior of hnRNPA1 from molecular simulations.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
157

Datenquelle: Europe PubMed Central

Abstract
Intrinsically disordered proteins (IDPs) are essential components for the formation of membraneless organelles, which play key functional and regulatory roles within biological systems. These complex assemblies form and dissolve spontaneously over time via liquid-liquid phase separation of IDPs. Mutations in their amino acid sequence can alter their phase behavior, which has been linked to the emergence of severe diseases. We study the conformation and phase behavior of a low-complexity domain of heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) using coarse-grained implicit solvent molecular dynamics simulations. We systematically analyze how these properties are affected by the number of aromatic residues within the examined sequences. We find a significant compaction of the chains and an increase in the critical temperature with an increasing number of aromatic residues. The local persistence length is determined in single-chain simulations, revealing strong sequence-specific variations along the chain contour. Comparing single-chain and condensed-state simulations, we find many more collapsed polymer conformations in the dilute systems, even at temperatures near the estimated θ-temperature of the solution. These observations strongly support the hypothesis that aromatic residues play a dominant role in condensation, which is further corroborated by a detailed analysis of the intermolecular contacts, and conversely that important properties of condensates are captured in coarse-grained simulations. Interestingly, we observe density inhomogeneities within the condensates near criticality, which are driven by electrostatic interactions. Finally, we find that the relatively small fraction of hydrophobic residues in the IDPs results in interfacial tensions, which are significantly lower compared to typical combinations of immiscible simple liquids.
Autoren
  • D Janka Bauer
  • Lukas S Stelzl
  • Arash Nikoubashman
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/36272811
DOI
10.1063/5.0105540
eISSN
1089-7690
Ausgabe der Veröffentlichung
15
Zeitschrift
J Chem Phys
Schlüsselwörter
  • Intrinsically Disordered Proteins
  • Heterogeneous Nuclear Ribonucleoprotein A1
  • Biochemical Phenomena
  • Polymers
  • Solvents
Sprache
eng
Country
United States
Paginierung
154903
Datum der Veröffentlichung
2022
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2022
Titel
Single-chain and condensed-state behavior of hnRNPA1 from molecular simulations.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
157

Datenquelle: PubMed

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