Evidence map›Paper›PMID 34301955›Full record

ArticleNature communications2021

A multi-step nucleation process determines the kinetics of prion-like domain phase separation.

Erik W Martin, Tyler S Harmon, Jesse B Hopkins, Srinivas Chakravarthy, J Jeremías Incicco, Peter Schuck, Andrea Soranno, Tanja Mittag

Abstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

73 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. α-Synuclein Forms Distinct Micelle-Like Assemblies at Low Ionic Strengths.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  5. Beyond equilibrium in biomolecular phase separation.Nature structural & molecular biology · 2026
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Nucleation Kinetics Reveals a Distinct Biological Function Space of Biomolecular Condensates.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  14. Review
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Article

13 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Erik W MartinDepartment of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN, USA. erik.martin@stjude.org.ORCID 0000-0002-8938-5001
Tyler S HarmonThe Max Planck Institute for the Physics of Complex Systems, Dresden, Germany.
Jesse B HopkinsThe Biophysics Collaborative Access Team (BioCAT), Department of Biological Sciences, Illinois Institute of Technology, Chicago, IL, USA.ORCID 0000-0001-8554-8072
Srinivas ChakravarthyThe Biophysics Collaborative Access Team (BioCAT), Department of Biological Sciences, Illinois Institute of Technology, Chicago, IL, USA.
J Jeremías InciccoDepartment of Biochemistry and Molecular Biophysics, Washington University in St. Louis, St. Louis, MO, USA.
Peter SchuckDynamics of Macromolecular Assembly Section, Laboratory of Cellular Imaging and Macromolecular Biophysics, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0002-8859-6966
Andrea SorannoDepartment of Biochemistry and Molecular Biophysics, Washington University in St. Louis, St. Louis, MO, USA.ORCID 0000-0001-8394-7993
Tanja MittagDepartment of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN, USA. tanja.mittag@stjude.org.ORCID 0000-0002-1827-3811

Funding

Time resolved SAXS studies on the RP2/Arl3 complex pp.484-485P41GM103622 · NIGMS · ILLINOIS INSTITUTE OF TECHNOLOGY · PI IRVING, THOMAS C · 2012 to 2020
$11.9M
Dynamics of Protein Assemblies by Analytical UltracentrifugationZIAEB000051 · NIBIB · NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING · PI SCHUCK, PETER · 2009 to 2025
$7.9M
Understanding the Sequence and Structural Determinants of Phase Behavior of ALS-Causing ProteinsR01NS121114 · NINDS · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI Tanja Mittag, ROHIT V PAPPU · 2021 to 2026
$3.8M
Advanced Pixel Array Detector for Time-Resolved SAXS and Fiber DiffractionS10OD018090 · OD · ILLINOIS INSTITUTE OF TECHNOLOGY · PI IRVING, THOMAS C · 2014 to 2014
$529k
NIGMS NIH HHS P41 GM103622NIH HHS S10 OD018090NINDS NIH HHS R01 NS121114
6 · The paper itself

Abstract

Compartmentalization by liquid-liquid phase separation (LLPS) has emerged as a ubiquitous mechanism underlying the organization of biomolecules in space and time. Here, we combine rapid-mixing time-resolved small-angle X-ray scattering (SAXS) approaches to characterize the assembly kinetics of a prototypical prion-like domain with equilibrium techniques that characterize its phase boundaries and the size distribution of clusters prior to phase separation. We find two kinetic regimes on the micro- to millisecond timescale that are distinguished by the size distribution of clusters. At the nanoscale, small complexes are formed with low affinity. After initial unfavorable complex assembly, additional monomers are added with higher affinity. At the mesoscale, assembly resembles classical homogeneous nucleation. Careful multi-pronged characterization is required for the understanding of condensate assembly mechanisms and will promote understanding of how the kinetics of biological phase separation is encoded in biomolecules.

Indexed as

Scattering, Small AngleAlgorithmsKineticsMicroscopy, ConfocalModels, ChemicalPrionsProtein ConformationThermodynamicsX-Ray DiffractionPrions

Identifiers

PMID34301955
PMCPMC8302766

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.