Thermal proximity coaggregation for system-wide profiling of protein complex dynamics in cells

Research output: Contribution to journalArticle


Proteins differentially interact with each other across cellular states and conditions, but an efficient proteome-wide strategy to monitor them is lacking. We report the application of thermal proximity coaggregation (TPCA) for high-throughput intracellular monitoring of protein complex dynamics. Significant TPCA signatures observed among well-validated protein-protein interactions correlate positively with interaction stoichiometry and are statistically observable in more than 350 annotated human protein complexes. Using TPCA, we identified many complexes without detectable differential protein expression, including chromatin-associated complexes, modulated in S phase of the cell cycle. Comparison of six cell lines by TPCA revealed cell-specific interactions even in fundamental cellular processes. TPCA constitutes an approach for system-wide studies of protein complexes in nonengineered cells and tissues and might be used to identify protein complexes that are modulated in diseases.


  • Chris Soon Heng Tan
  • Ka Diam Go
  • Xavier Bisteau
  • Lingyun Dai
  • Chern Han Yong
  • Nayana Prabhu
  • Mert Burak Ozturk
  • Yan Ting Lim
  • Lekshmy Sreekumar
  • Johan Lengqvist
  • Vinay Tergaonkar
  • Philipp Kaldis
  • Radoslaw M Sobota
  • Pär Nordlund
External organisations
  • A*STAR Institute of Medical Biology (IMB)
  • Nanyang Technological University
  • A*Star Institute of Molecular and Cell Biology (IMCB)
  • Duke–NUS Medical School
  • National University of Singapore
  • Karolinska Institutet
  • University of South Australia
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology


  • Cell Line, Cells, Chromatin/metabolism, Hot Temperature, Humans, Multiprotein Complexes/metabolism, Protein Aggregates, Protein Aggregation, Pathological/metabolism, Protein Array Analysis, Protein Biosynthesis, Protein Folding, Proteome
Original languageEnglish
Pages (from-to)1170-1177
Number of pages8
JournalScience (New York, N.Y.)
Issue number6380
Publication statusPublished - 2018 Mar 9
Publication categoryResearch
Externally publishedYes

Bibliographic note

Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.