Skip to content
DraconiticResearch
Search Sources API
203,234 studies31 sourcesUpdated 1 h ago
Peer-reviewedCC BY-NC-NDNature Communications

Proteome-scale quantification of the interactions driving condensate formation of intrinsically disordered proteins

  • Rasmus K. Norrild1
  • Sören von Bülow2
  • Baptiste Zanchet1
  • Einar Halldorsson1
  • Kresten Lindorff‐Larsen2
  • Joseph M. Rogers3
  • Alexander Kai Buell4
4 affiliations
  1. 1Department of Biotechnology and Biomedicine, Technical University of Denmark, Kgs. Lyngby, Denmark
  2. 2Department of Biology, University of Copenhagen, Copenhagen, Denmark
  3. 3Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark. [email protected]
  4. 4Department of Biotechnology and Biomedicine, Technical University of Denmark, Kgs. Lyngby, Denmark. [email protected]
Open at sourcePDFDOICite

Abstract

Cellular organization in the form of biomolecular condensates is a fundamental regulatory mechanism across all forms of life. Formation of condensates relies on multivalent interactions that are often weak and transient, making them challenging to study experimentally. We have developed Condensate Partitioning by mRNA-Display (CPmD) to measure these interactions from the partition free energies of peptides and nucleic acids into reconstituted condensates. CPmD increases experimental throughput by several orders of magnitude, and we apply it to reveal the interactions driving condensate formation of intrinsically disordered proteins. We show that the partition free energies of about one hundred thousand peptides derived from the disordered proteome into a model condensate directly reflect their intrinsic propensity to form condensates. We reveal that amino acid content, linked to hydrophobicity, is the primary determinant of phase behavior. Additionally, CPmD uniquely resolves subtle sequence-dependent contributions that can encode specificity. CPmD thus provides a powerful tool to decipher how weak interactions between protein and RNA regulate biological function through condensate formation.

Related

  1. Mapping interactions between disordered regions reveals promiscuity in biomolecular condensate formation
    Atar Gilat, Alexander I. Alexandrov, Benjamin Dubreuil +1
    Nature CommunicationsPeer-reviewedCC BY-NC-ND10 citedMolecular biology & gene regulationOpenAlex
  2. How a Highly Acidic SH3 Domain Binds to Its Intrinsically Disordered Partner through the Formation of an Encounter Complex Intermediate.
    Valeria Jaramillo-Martinez, Ritika Kukreja, Michaela R Cohen +15
    The journal of physical chemistry. BPeer-reviewedCC BYFull textMolecular biology & gene regulationEurope PMC
  3. Molecular Grammar of Intrinsically Disordered Regions: How Sequence and Context Shape Biomolecular Condensation and Disease
    Wei Liu, Sulin Lou
    BiomoleculesPeer-reviewedCC BYFull textGeneral biochemistryEurope PMC
  4. The intrinsically disordered N-terminal region of eIF5B nucleates RNA-driven phase separation
    B. K. Bodley-Gomes, M. T. Marr
    bioRxivPreprintAll rights reservedFull textGeneral biochemistrybioRxiv
  5. Conformational dynamics of an intrinsically disordered receptor enable signal transduction
    Y. Myokan, H. Zhang, T. Hongu +8
    bioRxivPreprintAll rights reservedFull textBiophysicsbioRxiv

Cite

BibTeXRIS
BibTeX
@article{norrild2026proteomescale,
  title = {{Proteome-scale quantification of the interactions driving condensate formation of intrinsically disordered proteins}},
  author = {Rasmus K. Norrild and Sören von Bülow and Baptiste Zanchet and Einar Halldorsson and Kresten Lindorff‐Larsen and Joseph M. Rogers and Alexander Kai Buell},
  journal = {Nature Communications},
  year = {2026},
  month = jul,
  doi = {10.1038/s41467-026-74825-z},
  url = {https://doi.org/10.1038/s41467-026-74825-z},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Proteome-scale quantification of the interactions driving condensate formation of intrinsically disordered proteins
AU  - Rasmus K. Norrild
AU  - Sören von Bülow
AU  - Baptiste Zanchet
AU  - Einar Halldorsson
AU  - Kresten Lindorff‐Larsen
AU  - Joseph M. Rogers
AU  - Alexander Kai Buell
PY  - 2026
DA  - 2026/07/09
JO  - Nature Communications
DO  - 10.1038/s41467-026-74825-z
UR  - https://doi.org/10.1038/s41467-026-74825-z
AB  - Cellular organization in the form of biomolecular condensates is a fundamental regulatory mechanism across all forms of life. Formation of condensates relies on multivalent interactions that are often weak and transient, making them challenging to study experimentally. We have developed Condensate Partitioning by mRNA-Display (CPmD) to measure these interactions from the partition free energies of peptides and nucleic acids into reconstituted condensates. CPmD increases experimental throughput by several orders of magnitude, and we apply it to reveal the interactions driving condensate formation of intrinsically disordered proteins. We show that the partition free energies of about one hundred thousand peptides derived from the disordered proteome into a model condensate directly reflect their intrinsic propensity to form condensates. We reveal that amino acid content, linked to hydrophobicity, is the primary determinant of phase behavior. Additionally, CPmD uniquely resolves subtle sequence-dependent contributions that can encode specificity. CPmD thus provides a powerful tool to decipher how weak interactions between protein and RNA regulate biological function through condensate formation.
SN  - 2041-1723
ER  -