Capturing protein communities by structural proteomics in a thermophilic eukaryote: Structural systems biology of lysates

Panagiotis L. Kastritis, Francis J O'Reilly, Thomas Bock, Yuanyue Li, Matt Z. Rogon, Katarzyna Buczak, Natalie Romanov, Matthew J. Betts, Khanh Huy Bui, Wim J Hagen, Marco L Hennrich, Marie-Therese Mackmull, Juri Rappsilber, Robert B. Russell, Peer Bork, Martin Beck, Anne-Claude Gavin

Research output: Contribution to journalArticlepeer-review

Abstract

The arrangement of proteins into complexes is a key organizational principle for many cellular functions. Although the topology of many complexes has been systematically analyzed in isolation, their molecular sociology in situ remains elusive. Here, we show that crude cellular extracts of a eukaryotic thermophile, Chaetomium thermophilum, retain basic principles of cellular organization. Using a structural proteomics approach, we simultaneously characterized the abundance, interactions and structure of a third of the C. thermophilum proteome within these extracts. We identified 27 distinct protein communities that include 108 interconnected complexes, which dynamically associate with each other and functionally benefit from being in close proximity in the cell. Furthermore, we investigated the structure of fatty acid synthase within these extracts by cryoEM and this revealed multiple, flexible states of the enzyme in adaptation to its association with other complexes, thus exemplifying the need for in situ studies. As the components of the captured protein communities are known – at both the protein and complex level – this study constitutes another step forward towards a molecular understanding of subcellular organization.
Original languageEnglish
JournalMolecular Systems Biology
Early online date13 Jul 2017
DOIs
Publication statusE-pub ahead of print - 13 Jul 2017

Keywords

  • Computational modeling
  • cryo-electron microscopy
  • fatty acid synthase
  • interaction proteomics
  • metabolism

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