Capturing protein communities by structural proteomics in a thermophilic eukaryote |
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Authors: | 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 |
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Institution: | 1. European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany;2. Cell Networks, Bioquant & Biochemie Zentrum Heidelberg, Heidelberg University, Heidelberg, Germany;3. Department of Anatomy and Cell Biology, McGill University, Montreal, QC, Canada;4. Chair of Bioanalytics, Institute of Biotechnology, Technische Universit?t Berlin, Berlin, Germany;5. Wellcome Trust Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, UK |
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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 levels—this study constitutes another step forward toward a molecular understanding of subcellular organization. |
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Keywords: | computational modeling cryo‐electron microscopy fatty acid synthase interaction proteomics metabolon |
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