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Proteome‐wide structural analysis of PTM hotspots reveals large body of putative regulatory elements with predicted biological function
Author(s) -
Dewhurst Henry,
Torres Matthew
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.864.24
Subject(s) - allosteric regulation , proteome , computational biology , function (biology) , chemistry , identification (biology) , evolutionary biology , biology , biochemistry , ecology , receptor
Post‐translational modifications (PTMs) have repeatedly been shown to play vital roles in regulation of protein behavior through modulation of protein‐protein binding and recognition site interactions, allosteric regulation, and conformational switching. SAPH‐ire (Structural Analysis of PTM Hotspots) has been used effectively to reveal novel PTM regulatory elements in G protein families (Dewhurst et al., 2015). Here, we proceed by applying SAPH‐ire to the comprehensive set of eukaryotic protein families containing experimental PTM and 3D structure data. This experiment captures 1,864 protein families and includes more than 60,756 unique PTM sites organized into 40,493 PTM hotspots, of which 2,659 possess known biological function (data obtained from PhosphoSitePlus), analyzed across 51,000 crystalized molecular structures representing 1,080 different species. This PTM data set represents the largest quantitative structural analysis of PTMs to date, yet less than 1/3 of the publically available eukaryotic PTM sites available at the time of investigation. PTM hotspots with a known biological function undergo up to 6‐fold enrichment using SAPH‐ire ranking methods – consistent with pilot studies (Dewhurst et al., 2015). Moreover, a preliminary survey revealed greater than 90% of top‐ranked hotspots lacking functional evidence in our input data could be linked to biological function by in‐depth literature searches. Thus, ~10% of PTM hotspots predicted to be biologically impactful have yet to be verified experimentally and represent putative regulatory elements. Taken together, these results highlight SAPH‐ire's value as a predictive tool for the identification of biologically important PTMs. Support or Funding Information This work was funded by the Georgia Tech School of Biology (M.T.) as well as the National Institutes of Health grant 4R00 GM094533‐03 (to M.T.).