TAILIEUCHUNG - Báo cáo khoa học: NMR and molecular dynamics studies of an autoimmune myelin basic protein peptide and its antagonist Structural implications for the MHC II (I-Au)–peptide complex from docking calculations

Experimental autoimmune encephalomyelitis can be induced in susceptible animals by immunodominant deter-minants of myelin basic protein (MBP). To characterize the molecular features of antigenic sites important for designing experimental autoimmune encephalomyelitis suppressing molecules, we report structural studies, based on NMR experimental data in conjunction with molecular dynamic simulations, of the potent linear dodecapeptide epitope of guinea pig MBP, Gln74-Lys75-Ser76-Gln77-Arg78-Ser79-Gln80-Asp81-Glu82-Asn83-Pro84-Val85 [MBP(74–85)], and its antagonist analogue Ala81MBP(74–85) | Eur. J. Biochem. 271 3399-3413 2004 FEBS 2004 doi NMR and molecular dynamics studies of an autoimmune myelin basic protein peptide and its antagonist Structural implications for the MHC II I-Au -peptide complex from docking calculations Andreas G. Tzakos1. Patrick Fuchs2 Nico A J. van Nuland2 Anastasios Troaanis3 Theodore Tselios4 . b. . Spyros Deraos4 John Matsoukas4 Ioannis P. Gerothanassis1 and Alexandre M. J. J. Bonvin2 1 Department of Chemistry Section of Organic Chemistry and Biochemistry University of loannina Greece 2Bijvoet Center for Biomolecular Research Department of NMR Spectroscopy Utrecht the Netherlands 3Department of Biological Applications and Technologies University of Ioannina Greece 4Department of Chemistry University of Patras Greece Experimental autoimmune encephalomyelitis can be induced in susceptible animals by immunodominant determinants of myelin basic protein MBP . To characterize the molecular features of antigenic sites important for designing experimental autoimmune encephalomyelitis suppressing molecules we report structural studies based on NMR experimental data in conjunction with molecular dynamic simulations of the potent linear dodecapeptide epitope of guinea pig MBP Gln74-Lys75-Ser76-Gln77-Arg78-Ser79-Gln80-Asp81-Glu82-Asn83-Pro84-Val85 MBP 74-85 and its antagonist analogue Ala81MBP 74-85 . The two peptides were studied in both water and Me2SO in order to mimic solvent-dependent structural changes in MBP. The agonist MBP 74-85 adopts a compact conformation because of electrostatic interactions of Arg78 with the side chains of Asp81 and Glu82. Arg78 is locked in a well-defined conformation perpendicular to the peptide backbone which is practically solvent independent. These electrostatic interactions are however absent from the antagonist Ala81MBP 74-85 resulting in great flexibility of the side chain of Arg78. Sequence alignment of the two analogues with several species of MBP suggests a .

• Báo cáo khoa học
• Report medicine
• traditional medicine
• scientific reports
• Antimicrobial
• cell structure
• genetics
• medical knowledge
• medical research
• analysis of cytoplasmic
• oxidation
• Crystal structure
• bacteria
• hemoglobin
• medicine
• cell proliferation
• breast cancer
• chemical reaction
• gastric cancer
• hormone medicine
• tumor cells
• biochemical studies
• environmental medicine