title: Physicochemical sequence characteristics that influence S-palmitoylation propensity.
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.
authors: a Department of Molecular Medicine , University of South Florida , 12901 Bruce B. Downs Blvd., MDC 07, Tampa , FL 33612 , USA.
authors: Krishna D
authors: KD
authors: Reddy
authors: a Department of Molecular Medicine , University of South Florida , 12901 Bruce B. Downs Blvd., MDC 07, Tampa , FL 33612 , USA.
authors: Jashwanth
authors: J
authors: Malipeddi
authors: a Department of Molecular Medicine , University of South Florida , 12901 Bruce B. Downs Blvd., MDC 07, Tampa , FL 33612 , USA.
authors: Shelly
authors: S
authors: DeForte
authors: c Department of Computer Science and Informatics , Indiana University , Bloomington , IN 47405 , USA.
authors: Vikas
authors: V
authors: Pejaver
authors: c Department of Computer Science and Informatics , Indiana University , Bloomington , IN 47405 , USA.
authors: Predrag
authors: P
authors: Radivojac
authors: a Department of Molecular Medicine , University of South Florida , 12901 Bruce B. Downs Blvd., MDC 07, Tampa , FL 33612 , USA.|b Johnnie B. Byrd Alzheimer's Research Institute , University of South Florida , Tampa , FL 33612 , USA.
authors: Vladimir N
authors: VN
authors: Uversky
authors: a Department of Molecular Medicine , University of South Florida , 12901 Bruce B. Downs Blvd., MDC 07, Tampa , FL 33612 , USA.
authors: Robert J
authors: RJ
authors: Deschenes
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D055598:Chemical Phenomena; D019295:Computational Biology / Q000379:methods; D016384:Consensus Sequence; D003545:Cysteine / Q000737:chemistry / Q000378:metabolism*; D030562:Databases, Protein; D054878:Lipoylation; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D020543:Proteome / Q000737:chemistry / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D020543:Proteome; D003545:Cysteine
keywords: acyltransferase; intrinsically disordered protein; palmitoylation; palmitoylomics; post-translational modification