Zinc ion dependent B-cell epitope, associated with primary Sjogren's syndrome, resides within the putative zinc finger domain of Ro60kD autoantigen: Physical and immunologic properties

Επιστημονική δημοσίευση - Άρθρο Περιοδικού uoadl:3022627 20 Αναγνώσεις

Μονάδα:
Ερευνητικό υλικό ΕΚΠΑ
Τίτλος:
Zinc ion dependent B-cell epitope, associated with primary Sjogren's syndrome, resides within the putative zinc finger domain of Ro60kD autoantigen: Physical and immunologic properties
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
The Ro/La ribonucleoprotein (RNP) complex is composed of the proteins Ro60kD, Ro52kD, and La48kD that are in association with one small cytoplasmic RNA (YRNA). Specific protein-RNA and protein-protein interactions are thought to occur through the RNP and zinc-finger secondary structure elements of the Ro60kD protein. The aim of our study was to investigate the antigenic properties of the zinc finger domain of the Ro60KD autoantigen and its contribution to the formation of Ro/La RNP complex. It was found that the peptide VSLVCEKLCNEKLLKKARIHPFHILIA (Zif-1), which corresponds to the natural sequence of the zinc finger domain (301-327), and the peptide C (Acm)NEKLLKKARIC(Acm), analogous to the intermediate loop 310-319 (Zif-3) of the same domain of Ro60KD, are recognized by the majority of anti-Ro/SSA and anti-La/SSB positive sera (82.6% and 77.1%, respectively) in the absence of zinc ions. The same sera failed to react with Zif-1 peptide in the presence of Zn2+. In contrast, the addition of zinc ions was necessary for the binding of Zif-1 to recombinant Ro52KD as shown by direct binding experiments of the recombinant protein with synthetic peptides. Our data suggest the zinc finger domain of Ro60kD contains a B-cell epitope with high specificity for primary Sjogren's syndrome. Furthermore, depending on the presence of zinc ions, the zinc finger domain of the Ro60KD protein can exist in two different conformational states favoring either an interaction with the Ro52KD protein or binding with autoantibodies.
Έτος δημοσίευσης:
2004
Συγγραφείς:
Routsias, J.G.
Kosmopoulou, A.
Makri, A.
Panou-Pomonis, E.
Sakarellos, C.
Sakarellos-Daitsiotis, M.
Moutsopoulos, H.M.
Tzioufas, A.G.
Περιοδικό:
Journal of Medicinal Chemistry
Τόμος:
47
Αριθμός / τεύχος:
17
Σελίδες:
4327-4334
Λέξεις-κλειδιά:
autoantibody; autoantigen; epitope; La SSB antibody; peptide derivative; protein La48kD; protein Ro52kD; protein Ro60kD; protein zif 1; recombinant protein; ribonucleoprotein; Ro antibody; small cytoplasmic RNA; synthetic peptide; unclassified drug; zinc finger protein; zinc ion, antigenicity; article; B lymphocyte; complex formation; human; protein conformation; protein domain; protein protein interaction; protein RNA binding; protein secondary structure; Sjoegren syndrome, Autoantibodies; Autoantigens; B-Lymphocytes; Cations, Divalent; Enzyme-Linked Immunosorbent Assay; Epitopes; Humans; Peptides; Protein Binding; Protein Conformation; Recombinant Proteins; Ribonucleoproteins; RNA, Small Cytoplasmic; Sjogren's Syndrome; Spectrometry, Mass, Electrospray Ionization; Zinc; Zinc Fingers
Επίσημο URL (Εκδότης):
DOI:
10.1021/jm049844+
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