Abstract:
:Biological systems are controlled by protein complexes that associate into dynamic protein interaction networks. We describe a strategy that analyzes protein complexes through the integration of label-free, quantitative mass spectrometry and computational analysis. By evaluating peptide intensity profiles throughout the sequential dilution of samples, the MasterMap system identifies specific interaction partners, detects changes in the composition of protein complexes and reveals variations in the phosphorylation states of components of protein complexes. We use the complexes containing the human forkhead transcription factor FoxO3A to demonstrate the validity and performance of this technology. Our analysis identifies previously known and unknown interactions of FoxO3A with 14-3-3 proteins, in addition to identifying FoxO3A phosphorylation sites and detecting reduced 14-3-3 binding following inhibition of phosphoinositide-3 kinase. By improving specificity and sensitivity of interaction networks, assessing post-translational modifications and providing dynamic interaction profiles, the MasterMap system addresses several limitations of current approaches for protein complexes.
journal_name
Nat Biotechnoljournal_title
Nature biotechnologyauthors
Rinner O,Mueller LN,Hubálek M,Müller M,Gstaiger M,Aebersold Rdoi
10.1038/nbt1289subject
Has Abstractpub_date
2007-03-01 00:00:00pages
345-52issue
3eissn
1087-0156issn
1546-1696pii
nbt1289journal_volume
25pub_type
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