|RAO, SHYAMA PRASAD - University Of Missouri|
|XU, DONG - University Of Missouri|
|THELEN, JAY - University Of Missouri|
Submitted to: BMC Bioinformatics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/29/2013
Publication Date: 10/13/2013
Publication URL: http://handle.nal.usda.gov/10113/58000
Citation: Rao, S.R., Xu, D., Thelen, J.J., Miernyk, J.A. 2013. Circles within circles: crosstalk between protein Ser/Thr/Tyr-phosphorylation and Met oxidation. BMC Bioinformatics. 14:S14.
Interpretive Summary: It is well-known that chemical modifications can control protein function. However the possible roles of interactions between different chemical modifications (crosstalk) in affecting protein function are not known. We have conducted an extensive mathematical and statistical analysis of protein sequences to assess the possibility of crosstalk between two distinct chemical modifications. The results indicate that there is the potential for protein chemical modification crosstalk in organisms representing all branches of the tree of life, from bacteria to man. Crosstalk is most likely in proteins involved with cellular signaling. Results from this study will be useful in understanding control of protein activity in crop plants, and will help to identify specific targets for modification by both breeders and molecular biologists. They will additionally be useful to scientists who study the effects of organ and tissue specialization in plant biology.
Technical Abstract: Background: Reversible posttranslational protein modifications such as phosphorylation of Ser/Thr/Tyr and Met oxidation are critical for both metabolic regulation and cellular signalling. Although these modifications are typically studied individually, herein we describe the potential for cross-talk and hierarchical regulation. Results: The proximity of Met to Ser/Thr/Tyr within the proteome has not previously been addressed. In order to consider the possibility of a generalized interaction, we performed a trans-kingdom sequence analysis of known phosphorylation sites in proteins from bacteria, fungi, plants, and animals. The proportion of phosphorylation sites that include a Met within a 13-residue window centered upon Ser/Thr/Tyr is significantly less than the occurrence of Met in proximity to all Ser/Thr/Tyr residues. Met residues are present at all positions (-6 to +6, inclusive) within the 13-residue window that we have considered. Detailed analysis of sequences from eight disparate plant taxa revealed that many conserved phosphorylation 15 sites have a Met residue in the proximity. Results from GO enrichment analysis indicated that the potential for phosphorylation and Met oxidation crosstalk is most prevalent in kinases and proteins involved in signaling. Conclusion: The large proportion of known phosphorylation sites with Met in the proximity fulfils the necessary condition for cross-talk. Kinases/signalling proteins are enriched for Met around phosphorylation sites. These proteins/sites are likely candidates for cross-talk between oxidative signalling and reversible phosphorylation.