Phosphorylated and nonphosphorylated epitopes of the La/SSB autoantigen: Comparison of their antigenic and conformational characteristics (Journal article)
Coudevylle, N./ Rokas, D./ Sakarellos-Daitsiotis, M./ Krikorian, D./ Panou-Pomonis, E./ Sakarellos, C./ Boussard, G./ Cung, M. T.
La/SSB phosphoprotein is the target antigen of autoantibodies in sera of patients with Sjogren'syndrome (SS) and systemic lupus erythematosus (SLE). Among other structural and junction motifs, four phosphorylation sites are encompassed in the primary sequence of La/SSB. Two of them (Thr-362 and Ser-366) are located within GSGKGKVQFQGKKTKFASDD (346-368) and one (Thr-302) within VTWEVLEGEVEKEALKKI (301-318), which are main B-cell epitopes of La/SSB. With the aim to investigate how phosphorylation, one of the most common posttranslational protein modifications, affects the antigenic and conformational characteristics of the La/SSB epitopes, we synthesized and studied the phosphorylated epitopes La/SSB(346-368)-P, La/SSB(359-368)-P, and La/SSB(301-318)-P with respect to their nonphosphorylated counterparts. Anti-La/SSB positive sera from SS and SLE patients are better recognized by the phosphorylated epitopes compared to their nonphosphorylated counterparts. Conformational analysis by 111 nuclear magnetic resonance spectroscopy and molecular dynamics showed that the phosphorylated epitopes adopt different structural characteristics from those of the corresponding nonphosphorylated epitopes. It is concluded that phosphorylation can create neoepitopes with altered functions, compared to the nonphosphorylated epitopes, which might be seen from the immune system as "foreign." (c) 2006 Wiley Periodicals, Inc.
|Institution and School/Department of submitter:||Πανεπιστήμιο Ιωαννίνων. Σχολή Θετικών Επιστημών. Τμήμα Χημείας|
|Keywords:||h-1 nuclear magnetic resonance spectroscopy,molecular dynamics simulation,nuclear overhauser enhancement spectroscopy,la/ssb autoantigen,phosphorylated epitopes of la/ssb,magnetic-resonance spectroscopy,systemic lupus-erythematosus,rna-polymerase iii,la ss-b,3-dimensional structures,cellular uptake,protein,peptides,classification,autoantibodies|
|Link:||<Go to ISI>://000238142200002|
|Appears in Collections:||Άρθρα σε επιστημονικά περιοδικά ( Ανοικτά)|
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