Article

From sequence to structural analysis in protein phosphorylation motifs

Biocomputing Group, Department of Biochemical Science A Rossi Fanelli, Sapienza University of Rome, P le Aldo Moro 5, Rome, Italy.
Frontiers in Bioscience (Impact Factor: 4.25). 01/2011; 16:1261-75. DOI: 10.2741/3787
Source: PubMed

ABSTRACT Phosphorylation is the most widely studied post-translational modification occurring in cells. While mass spectrometry-based proteomics experiments are uncovering thousands of novel in vivo phosphorylation sites, the identification of kinase specificity rules still remains a relatively slow and often inefficacious task. In the last twenty years, many efforts have being devoted to the experimental and computational identification of sequence and structural motifs encoding kinase-substrate interaction key residues and the phosphorylated amino acid itself. In this review, we retrace the road to the discovery of phosphorylation sequence motifs, examine the progresses achieved in the detection of three-dimensional motifs and discuss their importance in the understanding of regulation and de-regulation of many cellular processes.

0 Followers
 · 
149 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Phosphorylation offers a dynamic way to regulate protein activity and subcellular localization, which is achieved through its reversibility and fast kinetics. Adding or removing a dianionic phosphate group somewhere on a protein often changes the protein's structural properties, its stability and dynamics. Moreover, the majority of signaling pathways involve an extensive set of protein-protein interactions, and phosphorylation can be used to regulate and modulate protein-protein binding. Losses of phosphorylation sites, as a result of disease mutations, might disrupt protein binding and deregulate signal transduction. In this paper we focus on the effects of phosphorylation on protein stability, dynamics, and binding. We describe several physico-chemical mechanisms of protein regulation through phosphorylation and pay particular attention to phosphorylation in protein complexes and phosphorylation in the context of disorder-order and order-disorder transitions. Finally we assess the role of multiple phosphorylation sites in a protein molecule, their possible cooperativity and function.
    Frontiers in Genetics 08/2014; 5:270. DOI:10.3389/fgene.2014.00270
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Protein kinase CK2 is a critical regulator of several cellular and molecular signaling pathways. CK2 is unanimously distributed in eukaryotes and subsists in tetrameric complexes comprising two catalytic alpha and two regulatory beta subunits. Several reports have confirmed that protein kinase CK2 has great significance in diverse biological courses, particularly in cellular growth and proliferation in normal and disease conditions. However, in silico analysis of phosphorylation sites in the catalytic alpha subunit of CK2 remains to be elucidated. We described the distribution of predicted (neural network predictions for serine (S), threonine (T) and tyrosine(Y)) STY phosphorylation sites in CK2 alpha subunit of 15 multicellular and 2 unicellular organisms. We also showed the clustering of CK2 alpha subunit in these organisms using a phylogram. This data showed the prevalence of CK2 alpha subunits with potential STY phophorylation sites in several eukaryotic unicellular and mulicellular organisms that could be significant in the context of enigmatic protein kinase activities of CK2, enzyme-substrate interactions, further ligand-binding studies and new therapeutic interventions.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The Phospho.ELM resource (http://phospho.elm.eu.org) is a relational database designed to store in vivo and in vitro phosphorylation data extracted from the scientific literature and phosphoproteomic analyses. The resource has been actively developed for more than 7 years and currently comprises 42,574 serine, threonine and tyrosine non-redundant phosphorylation sites. Several new features have been implemented, such as structural disorder/order and accessibility information and a conservation score. Additionally, the conservation of the phosphosites can now be visualized directly on the multiple sequence alignment used for the score calculation. Finally, special emphasis has been put on linking to external resources such as interaction networks and other databases.
    Nucleic Acids Research 01/2011; 39(Database issue):261-267. DOI:10.1093/nar/gkq1104 · 8.81 Impact Factor

Preview

Download
5 Downloads
Available from