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==COMPLEX BETWEEN FV ANTIBODY FRAGMENT AND AN ANALOGUE OF THE MAIN IMMUNOGENIC REGION OF THE ACETYLCHOLINE RECEPTOR==
==COMPLEX BETWEEN FV ANTIBODY FRAGMENT AND AN ANALOGUE OF THE MAIN IMMUNOGENIC REGION OF THE ACETYLCHOLINE RECEPTOR==
<StructureSection load='1f3r' size='340' side='right'caption='[[1f3r]], [[NMR_Ensembles_of_Models | 1 NMR models]]' scene=''>
<StructureSection load='1f3r' size='340' side='right'caption='[[1f3r]]' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1f3r]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1F3R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1F3R FirstGlance]. <br>
<table><tr><td colspan='2'>[[1f3r]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1F3R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1F3R FirstGlance]. <br>
</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=NLE:NORLEUCINE'>NLE</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NLE:NORLEUCINE'>NLE</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1f3r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1f3r OCA], [https://pdbe.org/1f3r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1f3r RCSB], [https://www.ebi.ac.uk/pdbsum/1f3r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1f3r ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1f3r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1f3r OCA], [https://pdbe.org/1f3r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1f3r RCSB], [https://www.ebi.ac.uk/pdbsum/1f3r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1f3r ProSAT]</span></td></tr>
</table>
</table>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1f3r ConSurf].
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1f3r ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Binding of autoantibodies to the acetylcholine receptor (AChR) plays a major role in the autoimmune disease Myasthenia gravis (MG). In this paper, we propose a structure model of a putative immunocomplex that gives rise to the reduction of functional AChR molecules during the course of MG. The model complex consists of the [G(70), Nle(76)] decapeptide analogue of the main immunogenic region (MIR), representing the major antigenic epitope of AChR, and the single chain Fv fragment of monoclonal antibody 198, a potent MG autoantibody. The structure of the complexed decapeptide antigen [G(70), Nle(76)]MIR was determined using two-dimensional nmr, whereas the antibody structure was derived by means of homology modeling. The final complex was constructed using calculational docking and molecular dynamics. We termed this approach "directed modeling," since the known peptide structure directs the prestructured antibody binding site to its final conformation. The independently derived structures of the peptide antigen and antibody binding site already showed a high degree of surface complementarity after the initial docking calculation, during which the peptide was conformationally restrained. The docking routine was a soft algorithm, applying a combination of Monte Carlo simulation and energy minimization. The observed shape complementarity in the docking process suggested that the structure assessments already led to anti-idiotypic conformations of peptide antigen and antibody fragment. Refinement of the complex by dynamic simulation yielded improved surface adaptation by small rearrangements within antibody and antigen. The complex presented herein was analyzed in terms of antibody-antigen interactions, properties of contacting surfaces, and segmental mobility. The structural requirements for AChR complexation by autoantibodies were explored and compared with experimental data from alanine scans of the MIR peptides. The analysis revealed that the N-terminal loop of the peptide structure, which is indispensable for antibody recognition, aligns three hydrophobic groups in a favorable arrangement leading to the burial of 40% of the peptide surface in the binding cleft upon complexation. These data should be valuable in the rational design of an Fv mutant with much improved affinity for the MIR and AChR to be used in therapeutic approaches in MG.
The third-dimensional structure of the complex between an Fv antibody fragment and an analogue of the main immunogenic region of the acetylcholine receptor: a combined two-dimensional NMR, homology, and molecular modeling approach.,Kleinjung J, Petit MC, Orlewski P, Mamalaki A, Tzartos SJ, Tsikaris V, Sakarellos-Daitsiotis M, Sakarellos C, Marraud M, Cung MT Biopolymers. 2000 Feb;53(2):113-28. PMID:10679615<ref>PMID:10679615</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1f3r" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
[[Category: Cung, M T]]
[[Category: Cung M-T]]
[[Category: Kleinjung, J]]
[[Category: Kleinjung J]]
[[Category: Mamalaki, A]]
[[Category: Mamalaki A]]
[[Category: Marraud, M]]
[[Category: Marraud M]]
[[Category: Orlewski, P]]
[[Category: Orlewski P]]
[[Category: Petit, M C]]
[[Category: Petit M-C]]
[[Category: Sakarellos, C]]
[[Category: Sakarellos C]]
[[Category: Sakarellos-Daitsiotis, M]]
[[Category: Sakarellos-Daitsiotis M]]
[[Category: Tsikaris, V]]
[[Category: Tsikaris V]]
[[Category: Tzartos, S J]]
[[Category: Tzartos S-J]]
[[Category: Antibody-antigen]]
[[Category: Beta-turn]]
[[Category: Ig-fold]]
[[Category: Immune system]]
[[Category: Immuno complex]]

Revision as of 10:09, 20 March 2024

COMPLEX BETWEEN FV ANTIBODY FRAGMENT AND AN ANALOGUE OF THE MAIN IMMUNOGENIC REGION OF THE ACETYLCHOLINE RECEPTOR

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