Conformational studies of immunodominant myelin basic protein 1-11 analogues using NMR and molecular modeling (Journal article)
Laimou, D./ Lazoura, E./ Troganis, A. N./ Matsoukas, M. T./ Deraos, S. N./ Katsara, M./ Matsoukas, J./ Apostolopoulos, V./ Tselios, T. V.
Two dimensional nuclear magnetic resonance studies complimented by molecular dynamics simulations were conducted to investigate the conformation of the immunodominant epitope of acetylated myelin basic protein residues 1-11 (Ac-MBP(1-11)) and its altered peptide ligands, mutated at position 4 to an alanine (Ac-MBP(1-11)[4A]) or a tyrosine residue (Ac-MBP(1-11)[4Y]). Conformational analysis of the three analogues indicated that they adopt an extended conformation in DMSO solution as no long distance NOE connectivities were observed and seem to have a similar conformation when bound to the active site of the major histocompatibility complex (MHC II). The interaction of each peptide with MHC class II I-A(u) was further investigated in order to explore the molecular mechanism of experimental autoimmune encephalomyelitis induction/inhibition in mice. The present findings indicate that the Gln(3) residue, which serves as a T-cell receptor (TCR) contact site in the TCR/peptide/I-A(u) complex, has a different orientation in the mutated analogues especially in the Ac-MBP(1-11)[4A] peptide. In particular the side chain of Gln(3) is not solvent exposed as for the native Ac-MBP(1-11) and it is not available for interaction with the TCR.
|Institution and School/Department of submitter:||Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών και Τεχνολογιών. Τμήμα Βιολογικών Εφαρμογών και Τεχνολογιών|
|Keywords:||experimental autoimmune encephalomyelitis,multiple sclerosis,central nervous system,myelin basic protein,major histocompatibility complex class ii,t-cell receptor,experimental allergic encephalomyelitis,experimental autoimmune encephalomyelitis|
|Link:||<Go to ISI>://000298191200003|
|Appears in Collections:||Άρθρα σε επιστημονικά περιοδικά ( Ανοικτά)|
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