3bky

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[[Image:3bky.jpg|left|200px]]
 
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==Crystal Structure of Chimeric Antibody C2H7 Fab in complex with a CD20 Peptide==
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The line below this paragraph, containing "STRUCTURE_3bky", creates the "Structure Box" on the page.
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<StructureSection load='3bky' size='340' side='right'caption='[[3bky]], [[Resolution|resolution]] 2.61&Aring;' scene=''>
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[3bky]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BKY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BKY FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.61&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3bky FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bky OCA], [https://pdbe.org/3bky PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3bky RCSB], [https://www.ebi.ac.uk/pdbsum/3bky PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3bky ProSAT]</span></td></tr>
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{{STRUCTURE_3bky| PDB=3bky | SCENE= }}
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/CD20_HUMAN CD20_HUMAN] Defects in MS4A1 are the cause of immunodeficiency common variable type 5 (CVID5) [MIM:[https://omim.org/entry/613495 613495]; also called antibody deficiency due to CD20 defect. CVID5 is a primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen. The defect results from a failure of B-cell differentiation and impaired secretion of immunoglobulins; the numbers of circulating B-cells is usually in the normal range, but can be low.<ref>PMID:20038800</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/CD20_HUMAN CD20_HUMAN] This protein may be involved in the regulation of B-cell activation and proliferation.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bk/3bky_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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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=3bky ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Anti-CD20 monoclonal antibodies have been proven to be efficient in the treatment of certain B-cell lymphomas and autoimmune diseases. Intriguingly, these antibodies seem to exert diverse functions with narrow epitope specificity. This study is to investigate the molecular basis of the fine specificity of 2H7 derived antibodies which are of great therapeutic potential. We show that chimeric 2H7 (C2H7) can mediate complement dependent cytotoxicity and antibody-dependent cellular cytotoxicity effects on CD20 positive human Burkitt lymphoma cells and the Fab fragment can well recognize and bind to an epitope peptide of the extracellular loop of CD20. The crystal structure of C2H7 in complex with the CD20 epitope peptide was determined at 2.6A resolution. The bound peptide displays a circular conformation and the binding specificity is mainly contributed by the (170)ANPS(173) motif and the disulfide bond of the peptide which maintains the unique conformation of the peptide. Compared with the complex structure of another anti-CD20 monoclonal antibody Rituximab with the same epitope peptide which was previously determined, the major differences lie in the CDR loop H3 of C2H7 which stretches outward against the interface. Correspondingly, the pocket which accommodates the peptide becomes wider and the peptide moves toward loop H3 and thus is more distant from loops H1 and H2. The hydrogen-bonding interactions are also quite different from those observed in the Rituximab-epitope peptide complex, and both the hydrophilic and hydrophobic interactions are less intense. Our data not only reveal the molecular basis for the fine specificity of C2H7 to CD20, but also provide valuable information for further improvement of antibodies derived from 2H7.
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'''Crystal Structure of Chimeric Antibody C2H7 Fab in complex with a CD20 Peptide'''
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Crystal structure of chimeric antibody C2H7 Fab in complex with a CD20 peptide.,Du J, Wang H, Zhong C, Peng B, Zhang M, Li B, Hou S, Guo Y, Ding J Mol Immunol. 2008 May;45(10):2861-8. Epub 2008 Mar 17. PMID:18346788<ref>PMID:18346788</ref>
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==Overview==
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Anti-CD20 monoclonal antibodies have been proven to be efficient in the treatment of certain B-cell lymphomas and autoimmune diseases. Intriguingly, these antibodies seem to exert diverse functions with narrow epitope specificity. This study is to investigate the molecular basis of the fine specificity of 2H7 derived antibodies which are of great therapeutic potential. We show that chimeric 2H7 (C2H7) can mediate complement dependent cytotoxicity and antibody-dependent cellular cytotoxicity effects on CD20 positive human Burkitt lymphoma cells and the Fab fragment can well recognize and bind to an epitope peptide of the extracellular loop of CD20. The crystal structure of C2H7 in complex with the CD20 epitope peptide was determined at 2.6A resolution. The bound peptide displays a circular conformation and the binding specificity is mainly contributed by the (170)ANPS(173) motif and the disulfide bond of the peptide which maintains the unique conformation of the peptide. Compared with the complex structure of another anti-CD20 monoclonal antibody Rituximab with the same epitope peptide which was previously determined, the major differences lie in the CDR loop H3 of C2H7 which stretches outward against the interface. Correspondingly, the pocket which accommodates the peptide becomes wider and the peptide moves toward loop H3 and thus is more distant from loops H1 and H2. The hydrogen-bonding interactions are also quite different from those observed in the Rituximab-epitope peptide complex, and both the hydrophilic and hydrophobic interactions are less intense. Our data not only reveal the molecular basis for the fine specificity of C2H7 to CD20, but also provide valuable information for further improvement of antibodies derived from 2H7.
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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3BKY is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens,_mus_musculus Homo sapiens, mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BKY OCA].
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</div>
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<div class="pdbe-citations 3bky" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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Crystal structure of chimeric antibody C2H7 Fab in complex with a CD20 peptide., Du J, Wang H, Zhong C, Peng B, Zhang M, Li B, Hou S, Guo Y, Ding J, Mol Immunol. 2008 May;45(10):2861-2868. Epub 2008 Mar 17. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18346788 18346788]
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*[[Antibody 3D structures|Antibody 3D structures]]
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[[Category: Homo sapiens, mus musculus]]
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*[[3D structures of non-human antibody|3D structures of non-human antibody]]
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[[Category: Protein complex]]
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== References ==
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[[Category: Ding, J.]]
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<references/>
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[[Category: Du, J.]]
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__TOC__
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[[Category: Zhong, C.]]
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</StructureSection>
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[[Category: 2h7]]
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[[Category: Homo sapiens]]
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[[Category: B-cell activation]]
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[[Category: Large Structures]]
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[[Category: C2h7]]
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[[Category: Ding J]]
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[[Category: Cd20]]
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[[Category: Du J]]
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[[Category: Chimeric antibody]]
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[[Category: Zhong C]]
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[[Category: Fab]]
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[[Category: Fab-peptide complex]]
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[[Category: Immune system]]
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[[Category: Membrane]]
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[[Category: Pharmaceutical]]
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[[Category: Phosphoprotein]]
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[[Category: Transmembrane]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Apr 30 13:32:57 2008''
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Current revision

Crystal Structure of Chimeric Antibody C2H7 Fab in complex with a CD20 Peptide

PDB ID 3bky

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