Capturing protein communities by structural proteomics in a thermophilic eukaryote
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...
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| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2017-07-01
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| Series: | Molecular Systems Biology |
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| Online Access: | https://doi.org/10.15252/msb.20167412 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Panagiotis L Kastritis |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-15f6ec5f9421498ca23ca26e8be3eb20 |
| institution | Kabale University |
| issn | 1744-4292 |
| language | English |
| publishDate | 2017-07-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-15f6ec5f9421498ca23ca26e8be3eb202025-08-20T03:46:37ZengSpringer NatureMolecular Systems Biology1744-42922017-07-0113711410.15252/msb.20167412Capturing protein communities by structural proteomics in a thermophilic eukaryotePanagiotis L Kastritis0Francis J O'Reilly1Thomas Bock2Yuanyue Li3Matt Z Rogon4Katarzyna Buczak5Natalie Romanov6Matthew J Betts7Khanh Huy Bui8Wim J Hagen9Marco L Hennrich10Marie‐Therese Mackmull11Juri Rappsilber12Robert B Russell13Peer Bork14Martin Beck15Anne‐Claude Gavin16European Molecular Biology Laboratory, Structural and Computational Biology UnitEuropean Molecular Biology Laboratory, Structural and Computational Biology UnitEuropean Molecular Biology Laboratory, Structural and Computational Biology UnitEuropean Molecular Biology Laboratory, Structural and Computational Biology UnitEuropean Molecular Biology Laboratory, Structural and Computational Biology UnitEuropean Molecular Biology Laboratory, Structural and Computational Biology UnitEuropean Molecular Biology Laboratory, Structural and Computational Biology UnitCell Networks, Bioquant & Biochemie Zentrum Heidelberg, Heidelberg UniversityEuropean Molecular Biology Laboratory, Structural and Computational Biology UnitEuropean Molecular Biology Laboratory, Structural and Computational Biology UnitEuropean Molecular Biology Laboratory, Structural and Computational Biology UnitEuropean Molecular Biology Laboratory, Structural and Computational Biology UnitChair of Bioanalytics, Institute of Biotechnology, Technische Universität BerlinCell Networks, Bioquant & Biochemie Zentrum Heidelberg, Heidelberg UniversityEuropean Molecular Biology Laboratory, Structural and Computational Biology UnitEuropean Molecular Biology Laboratory, Structural and Computational Biology UnitEuropean Molecular Biology Laboratory, Structural and Computational Biology UnitAbstract 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.https://doi.org/10.15252/msb.20167412computational modelingcryo‐electron microscopyfatty acid synthaseinteraction proteomicsmetabolon |
| spellingShingle | 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 Capturing protein communities by structural proteomics in a thermophilic eukaryote Molecular Systems Biology computational modeling cryo‐electron microscopy fatty acid synthase interaction proteomics metabolon |
| title | Capturing protein communities by structural proteomics in a thermophilic eukaryote |
| title_full | Capturing protein communities by structural proteomics in a thermophilic eukaryote |
| title_fullStr | Capturing protein communities by structural proteomics in a thermophilic eukaryote |
| title_full_unstemmed | Capturing protein communities by structural proteomics in a thermophilic eukaryote |
| title_short | Capturing protein communities by structural proteomics in a thermophilic eukaryote |
| title_sort | capturing protein communities by structural proteomics in a thermophilic eukaryote |
| topic | computational modeling cryo‐electron microscopy fatty acid synthase interaction proteomics metabolon |
| url | https://doi.org/10.15252/msb.20167412 |
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