title: Quantitative proteomics and network analysis of SSA1 and SSB1 deletion mutants reveals robustness of chaperone HSP70 network in Saccharomyces cerevisiae.
abstract: Molecular chaperones play an important role in protein homeostasis and the cellular response to stress. In particular, the HSP70 chaperones in yeast mediate a large volume of protein folding through transient associations with their substrates. This chaperone interaction network can be disturbed by various perturbations, such as environmental stress or a gene deletion. Here, we consider deletions of two major chaperone proteins, SSA1 and SSB1, from the chaperone network in Sacchromyces cerevisiae. We employ a SILAC-based approach to examine changes in global and local protein abundance and rationalise our results via network analysis and graph theoretical approaches. Although the deletions result in an overall increase in intracellular protein content, correlated with an increase in cell size, this is not matched by substantial changes in individual protein concentrations. Despite the phenotypic robustness to deletion of these major hub proteins, it cannot be simply explained by the presence of paralogues. Instead, network analysis and a theoretical consideration of folding workload suggest that the robustness to perturbation is a product of the overall network structure. This highlights how quantitative proteomics and systems modelling can be used to rationalise emergent network properties, and how the HSP70 system can accommodate the loss of major hubs.
authors.affiliation: Faculty of Life Sciences, Michael Smith Building, Manchester, UK.
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Jarnuczak
authors.affiliation: Centre for Proteome Research, Department of Biochemistry, Institute of Integrative Biology, University of Liverpool, Liverpool, UK.
authors.forename: Claire E
authors.initials: CE
authors.lastname: Eyers
authors.affiliation: Faculty of Life Sciences, Michael Smith Building, Manchester, UK.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Schwartz
authors.affiliation: Faculty of Life Sciences, Michael Smith Building, Manchester, UK.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Grant
authors.affiliation: Faculty of Life Sciences, Michael Smith Building, Manchester, UK.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Hubbard
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000378:metabolism; D017353:Gene Deletion; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D007553:Isotope Labeling; D009154:Mutation; D060066:Protein Interaction Maps; D040901:Proteomics; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D018840:HSP70 Heat-Shock Proteins; C095192:SSB1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D000251:Adenosine Triphosphatases; C095973:SSA1 protein, S cerevisiae
keywords: Betweenness centrality; Chaperones; Protein interaction networks; Quantitative proteomics; SILAC; Systems biology