Hydrogen bond guidance and aromatic stacking drive liquid-liquid phase separation of intrinsically disordered histidine-rich peptides
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- Bartosz Gabryelczyk
- Hao Cai
- Xiangyan Shi
- Yue Sun
- Piet JM Swinkels
- Stefan Salentinig
- Konstantin Pervushin
- Ali Miserez
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000500473800001&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1038/s41467-019-13469-8
- Externe Identifier
- Clarivate Analytics Document Solution ID: JS7HI
- PubMed Identifier: 31784535
- ISSN
- 2041-1723
- Zeitschrift
- NATURE COMMUNICATIONS
- Artikelnummer
- ARTN 5465
- Datum der Veröffentlichung
- 2019
- Status
- Published
- Titel
- Hydrogen bond guidance and aromatic stacking drive liquid-liquid phase separation of intrinsically disordered histidine-rich peptides
- Sub types
- Article
- Ausgabe der Zeitschrift
- 10
Data source: Web of Science (Lite)
- Other metadata sources:
-
- Abstract
- <jats:title>Abstract</jats:title><jats:p>Liquid-liquid phase separation (LLPS) of intrinsically disordered proteins (IDPs) is involved in both intracellular membraneless organelles and extracellular tissues. Despite growing understanding of LLPS, molecular-level mechanisms behind this process are still not fully established. Here, we use histidine-rich squid beak proteins (HBPs) as model IDPs to shed light on molecular interactions governing LLPS. We show that LLPS of HBPs is mediated though specific modular repeats. The morphology of separated phases (liquid-like versus hydrogels) correlates with the repeats’ hydrophobicity. Solution-state NMR indicates that LLPS is a multistep process initiated by deprotonation of histidine residues, followed by transient hydrogen bonding with tyrosine, and eventually by hydrophobic interactions. The microdroplets are stabilized by aromatic clustering of tyrosine residues exhibiting restricted molecular mobility in the nano-to-microsecond timescale according to solid-state NMR experiments. Our findings provide guidelines to rationally design pH-responsive peptides with LLPS ability for various applications, including bioinspired protocells and smart drug-delivery systems.</jats:p>
- Autoren
- Bartosz Gabryelczyk
- Hao Cai
- Xiangyan Shi
- Yue Sun
- Piet JM Swinkels
- Stefan Salentinig
- Konstantin Pervushin
- Ali Miserez
- DOI
- 10.1038/s41467-019-13469-8
- eISSN
- 2041-1723
- Ausgabe der Veröffentlichung
- 1
- Zeitschrift
- Nature Communications
- Sprache
- en
- Artikelnummer
- 5465
- Online publication date
- 2019
- Status
- Published online
- Herausgeber
- Springer Science and Business Media LLC
- Herausgeber URL
- http://dx.doi.org/10.1038/s41467-019-13469-8
- Datum der Datenerfassung
- 2022
- Titel
- Hydrogen bond guidance and aromatic stacking drive liquid-liquid phase separation of intrinsically disordered histidine-rich peptides
- Ausgabe der Zeitschrift
- 10
Data source: Crossref
- Abstract
- Liquid-liquid phase separation (LLPS) of intrinsically disordered proteins (IDPs) is involved in both intracellular membraneless organelles and extracellular tissues. Despite growing understanding of LLPS, molecular-level mechanisms behind this process are still not fully established. Here, we use histidine-rich squid beak proteins (HBPs) as model IDPs to shed light on molecular interactions governing LLPS. We show that LLPS of HBPs is mediated though specific modular repeats. The morphology of separated phases (liquid-like versus hydrogels) correlates with the repeats' hydrophobicity. Solution-state NMR indicates that LLPS is a multistep process initiated by deprotonation of histidine residues, followed by transient hydrogen bonding with tyrosine, and eventually by hydrophobic interactions. The microdroplets are stabilized by aromatic clustering of tyrosine residues exhibiting restricted molecular mobility in the nano-to-microsecond timescale according to solid-state NMR experiments. Our findings provide guidelines to rationally design pH-responsive peptides with LLPS ability for various applications, including bioinspired protocells and smart drug-delivery systems.
- Addresses
- Center for Biomimetic Sensor Science, School of Materials Science and Engineering, Nanyang Technological University (NTU), 50 Nanyang Drive, Singapore, 637553, Singapore.
- Autoren
- Bartosz Gabryelczyk
- Hao Cai
- Xiangyan Shi
- Yue Sun
- Piet JM Swinkels
- Stefan Salentinig
- Konstantin Pervushin
- Ali Miserez
- DOI
- 10.1038/s41467-019-13469-8
- eISSN
- 2041-1723
- Externe Identifier
- PubMed Identifier: 31784535
- PubMed Central ID: PMC6884462
- Funding acknowledgements
- Nanyang Technological University: Strategic Initiative on Biomimetic and Sustainable Materials (IBSM)
- Ministry of Education - Singapore: MOE2015-T2-1-062
- Open access
- true
- ISSN
- 2041-1723
- Ausgabe der Veröffentlichung
- 1
- Zeitschrift
- Nature communications
- Schlüsselwörter
- Beak
- Animals
- Biopolymers
- Tyrosine
- Histidine
- Biocompatible Materials
- Colloids
- Microscopy
- Magnetic Resonance Spectroscopy
- Protein Engineering
- Hydrogen Bonding
- Hydrogen-Ion Concentration
- Decapodiformes
- Scattering, Small Angle
- Hydrophobic and Hydrophilic Interactions
- Intrinsically Disordered Proteins
- Sprache
- eng
- Medium
- Electronic
- Online publication date
- 2019
- Open access status
- Open Access
- Paginierung
- 5465
- Datum der Veröffentlichung
- 2019
- Status
- Published
- Publisher licence
- CC BY
- Datum der Datenerfassung
- 2019
- Titel
- Hydrogen bond guidance and aromatic stacking drive liquid-liquid phase separation of intrinsically disordered histidine-rich peptides.
- Sub types
- Research Support, Non-U.S. Gov't
- research-article
- Journal Article
- Ausgabe der Zeitschrift
- 10
Files
https://www.nature.com/articles/s41467-019-13469-8.pdf https://europepmc.org/articles/PMC6884462?pdf=render
Data source: Europe PubMed Central
- Abstract
- Liquid-liquid phase separation (LLPS) of intrinsically disordered proteins (IDPs) is involved in both intracellular membraneless organelles and extracellular tissues. Despite growing understanding of LLPS, molecular-level mechanisms behind this process are still not fully established. Here, we use histidine-rich squid beak proteins (HBPs) as model IDPs to shed light on molecular interactions governing LLPS. We show that LLPS of HBPs is mediated though specific modular repeats. The morphology of separated phases (liquid-like versus hydrogels) correlates with the repeats' hydrophobicity. Solution-state NMR indicates that LLPS is a multistep process initiated by deprotonation of histidine residues, followed by transient hydrogen bonding with tyrosine, and eventually by hydrophobic interactions. The microdroplets are stabilized by aromatic clustering of tyrosine residues exhibiting restricted molecular mobility in the nano-to-microsecond timescale according to solid-state NMR experiments. Our findings provide guidelines to rationally design pH-responsive peptides with LLPS ability for various applications, including bioinspired protocells and smart drug-delivery systems.
- Date of acceptance
- 2019
- Autoren
- Bartosz Gabryelczyk
- Hao Cai
- Xiangyan Shi
- Yue Sun
- Piet JM Swinkels
- Stefan Salentinig
- Konstantin Pervushin
- Ali Miserez
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/31784535
- DOI
- 10.1038/s41467-019-13469-8
- eISSN
- 2041-1723
- Externe Identifier
- PubMed Central ID: PMC6884462
- Ausgabe der Veröffentlichung
- 1
- Zeitschrift
- Nat Commun
- Schlüsselwörter
- Animals
- Beak
- Biocompatible Materials
- Biopolymers
- Colloids
- Decapodiformes
- Histidine
- Hydrogen Bonding
- Hydrogen-Ion Concentration
- Hydrophobic and Hydrophilic Interactions
- Intrinsically Disordered Proteins
- Magnetic Resonance Spectroscopy
- Microscopy
- Protein Engineering
- Scattering, Small Angle
- Tyrosine
- Sprache
- eng
- Country
- England
- Paginierung
- 5465
- PII
- 10.1038/s41467-019-13469-8
- Datum der Veröffentlichung
- 2019
- Status
- Published online
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2020
- Titel
- Hydrogen bond guidance and aromatic stacking drive liquid-liquid phase separation of intrinsically disordered histidine-rich peptides.
- Sub types
- Journal Article
- Research Support, Non-U.S. Gov't
- Ausgabe der Zeitschrift
- 10
Data source: PubMed
- Beziehungen:
- Property of