Header

UZH-Logo

Maintenance Infos

Driving forces of the complex formation between highly charged disordered proteins


Chowdhury, Aritra; Borgia, Alessandro; Ghosh, Souradeep; Sottini, Andrea; Mitra, Soumik; Eapen, Rohan S; Borgia, Madeleine B; Yang, Tianjin; Galvanetto, Nicola; Ivanović, Miloš T; Łukijańczuk, Paweł; Zhu, Ruijing; Nettels, Daniel; Kundagrami, Arindam; Schuler, Benjamin (2023). Driving forces of the complex formation between highly charged disordered proteins. Proceedings of the National Academy of Sciences of the United States of America, 120(41):e2304036120.

Abstract

Highly disordered complexes between oppositely charged intrinsically disordered proteins present a new paradigm of biomolecular interactions. Here, we investigate the driving forces of such interactions for the example of the highly positively charged linker histone H1 and its highly negatively charged chaperone, prothymosin α (ProTα). Temperature-dependent single-molecule Förster resonance energy transfer (FRET) experiments and isothermal titration calorimetry reveal ProTα-H1 binding to be enthalpically unfavorable, and salt-dependent affinity measurements suggest counterion release entropy to be an important thermodynamic driving force. Using single-molecule FRET, we also identify ternary complexes between ProTα and H1 in addition to the heterodimer at equilibrium and show how they contribute to the thermodynamics observed in ensemble experiments. Finally, we explain the observed thermodynamics quantitatively with a mean-field polyelectrolyte theory that treats counterion release explicitly. ProTα-H1 complex formation resembles the interactions between synthetic polyelectrolytes, and the underlying principles are likely to be of broad relevance for interactions between charged biomolecules in general.

Abstract

Highly disordered complexes between oppositely charged intrinsically disordered proteins present a new paradigm of biomolecular interactions. Here, we investigate the driving forces of such interactions for the example of the highly positively charged linker histone H1 and its highly negatively charged chaperone, prothymosin α (ProTα). Temperature-dependent single-molecule Förster resonance energy transfer (FRET) experiments and isothermal titration calorimetry reveal ProTα-H1 binding to be enthalpically unfavorable, and salt-dependent affinity measurements suggest counterion release entropy to be an important thermodynamic driving force. Using single-molecule FRET, we also identify ternary complexes between ProTα and H1 in addition to the heterodimer at equilibrium and show how they contribute to the thermodynamics observed in ensemble experiments. Finally, we explain the observed thermodynamics quantitatively with a mean-field polyelectrolyte theory that treats counterion release explicitly. ProTα-H1 complex formation resembles the interactions between synthetic polyelectrolytes, and the underlying principles are likely to be of broad relevance for interactions between charged biomolecules in general.

Statistics

Citations

Dimensions.ai Metrics
4 citations in Web of Science®
5 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

2 downloads since deposited on 28 Nov 2023
2 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Department of Biochemistry
07 Faculty of Science > Department of Biochemistry
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Health Sciences > Multidisciplinary
Language:English
Date:5 October 2023
Deposited On:28 Nov 2023 09:55
Last Modified:29 Jun 2024 01:40
Publisher:National Academy of Sciences
ISSN:0027-8424
OA Status:Closed
Publisher DOI:https://doi.org/10.1073/pnas.2304036120
PubMed ID:37796987
Other Identification Number:PMCID: PMC10576128