Capturing protein communities by structural proteomics in a thermophilic eukaryote.
Kastritis PL, O'Reilly FJ, Bock T, Li YY
, Rogon MZ, Buczak K, Romanov N
, Betts MJ, Bui KH, Hagen WJ, Hennrich ML, Mackmull MT, Rappsilber J, Russell RB, Bork P
, Beck M, Gavin AC
Mol Syst Biol.
2017 Jul 25; 13(7): 936. PubMed: 28743795.
Abstract + PDF
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.