Hub proteins in interaction networks involved in signaling pathways are known to have more disordered residues than non-hubs. Since the signaling mechanisms involving PPI are regulated by phosphorylation, disordered interfaces could be thought to be extremely phosphorylated. In the present study we sought to map the phosphorylated sites onto disordered regions on interacting proteins-Interactomes and non-interacting proteins-Negatomes. Dataset of non-interacting protein included 784 proteins retrieved from Negatome database 2.0. 2252 interacting proteins were retrieved from “GeneMania”. Intrinsically disordered regions were predicted with “Disopred” program. The binding interfaces were defined by “PDBePISA” server, while, phosphorylation sites were derived from “NetPhos” program. All phosphorylation sites were mapped onto protein structures using alignments calculated by the MUSCLE program. As anticipated, the extent of phosphorylation in interactomes were significantly higher in disordered regions to its ordered counter parts (p=0.04). Insights revealed that the disordered regions in negatome were sparse in comparison to those in interactomes (p<0.0024). Declined phosphorylated sites were observed in negatomes. The widespread non-flexible and ordered regions in the negatomes confer the non interacting nature of the protein in turn makes it poor participant in signal transduction that involves phosphorylation. Our study sheds light on the importance of phosphorylated sites on disordered regions as a mark to decide whether protein would possibly interact or not.
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Phosphorylated Sites on the Disordered Interface Signatures the Interacting Behavior of Proteins - A Comparative Mapping of Phosphorylation Propensities on Disordered Interfaces of Interactome and Negatome
Published: 04 December 2015 by MDPI in MOL2NET'15, Conference on Molecular, Biomed., Comput. & Network Science and Engineering, 1st ed. congress CHEMBIO.MOL-01: Org. Chem., Med. Chem., Pharm. Industry, & Mol. Biol., Congress, Paris, France-Galveston, USA, 2023., Rostock, Germany-Bilbao, Spain-Galveston, Texas, USA, 2015
Keywords: Disordered regions, Phosphorylation sites, Interactomes, Negatomes