Physicochemical Sequence Characteristics that Influence S-palmitoylation Propensity
Document Type
Article
Publication Date
2017
Keywords
acyltransferase, palmitoylation, palmitoylomics, post-translational modification, intrinsically disordered protein
Digital Object Identifier (DOI)
https://doi.org/10.1080/07391102.2016.1217275
Abstract
Over the past 30 years, several hundred eukaryotic proteins spanning from yeast to man have been shown to be S-palmitoylated. This post-translational modification involves the reversible addition of a 16-carbon saturated fatty acyl chain onto the cysteine residue of a protein where it regulates protein membrane association and distribution, conformation, and stability. However, the large-scale proteome-wide discovery of new palmitoylated proteins has been hindered by the difficulty of identifying a palmitoylation consensus sequence. Using a bioinformatics approach, we show that the enrichment of hydrophobic and basic residues, the cellular context of the protein, and the structural features of the residues surrounding the palmitoylated cysteine all influence the likelihood of palmitoylation. We developed a new palmitoylation predictor that incorporates these identified features, and this predictor achieves a Matthews Correlation Coefficient of .74 using 10-fold cross validation, and significantly outperforms existing predictors on unbiased testing sets. This demonstrates that palmitoylation sites can be predicted with accuracy by taking into account not only physiochemical properties of the modified cysteine and its surrounding residues, but also structural parameters and the subcellular localization of the modified cysteine. This will allow for improved predictions of palmitoylated residues in uncharacterized proteins. A web-based version of this predictor is currently under development.
Was this content written or created while at USF?
Yes
Citation / Publisher Attribution
Journal of Biomolecular Structure and Dynamics, v. 35, issue 11, p. 2337-2350
Scholar Commons Citation
Reddy, Krishna D.; Malipeddi, Jashwanth; DeForte, Shelly; Pejaver, Vikas; Radivojac, Predrag; Uversky, Vladimir N.; and Deschenes, Robert J., "Physicochemical Sequence Characteristics that Influence S-palmitoylation Propensity" (2017). Molecular Medicine Faculty Publications. 272.
https://digitalcommons.usf.edu/mme_facpub/272
