|
|
| Line 3: |
Line 3: |
| | <StructureSection load='2osl' size='340' side='right'caption='[[2osl]], [[Resolution|resolution]] 2.60Å' scene=''> | | <StructureSection load='2osl' size='340' side='right'caption='[[2osl]], [[Resolution|resolution]] 2.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2osl]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OSL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2OSL FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2osl]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OSL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2OSL FirstGlance]. <br> |
| - | </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=2osl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2osl OCA], [https://pdbe.org/2osl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2osl RCSB], [https://www.ebi.ac.uk/pdbsum/2osl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2osl ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6Å</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=2osl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2osl OCA], [https://pdbe.org/2osl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2osl RCSB], [https://www.ebi.ac.uk/pdbsum/2osl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2osl ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[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>
| + | [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> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/CD20_HUMAN CD20_HUMAN]] This protein may be involved in the regulation of B-cell activation and proliferation.
| + | [https://www.uniprot.org/uniprot/CD20_HUMAN CD20_HUMAN] This protein may be involved in the regulation of B-cell activation and proliferation. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| Line 38: |
Line 39: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Ding, J]] | + | [[Category: Ding J]] |
| - | [[Category: Du, J]] | + | [[Category: Du J]] |
| - | [[Category: Zhong, C]] | + | [[Category: Zhong C]] |
| - | [[Category: Chimeric antibody]]
| + | |
| - | [[Category: Fab-peptide complex]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Rituximab]]
| + | |
| Structural highlights
Disease
CD20_HUMAN Defects in MS4A1 are the cause of immunodeficiency common variable type 5 (CVID5) [MIM: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.[1]
Function
CD20_HUMAN This protein may be involved in the regulation of B-cell activation and proliferation.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Rituximab is a widely used monoclonal antibody drug for treating certain lymphomas and autoimmune diseases. To understand the molecular mechanism of recognition of human CD20 by Rituximab, we determined the crystal structure of the Rituximab Fab in complex with a synthesized peptide comprising the CD20 epitope (residues 163-187) at 2.6-A resolution. The combining site of the Fab consists of four complementarity determining regions that form a large, deep pocket to accommodate the epitope peptide. The bound peptide assumes a unique cyclic conformation that is constrained by a disulfide bond and a rigid proline residue (Pro(172)). The (170)ANPS(173) motif of CD20 is deeply embedded into the pocket on the antibody surface and plays an essential role in the recognition and binding of Rituximab. The antigen-antibody interactions involve both hydrogen bonds and van der Waals contacts and display a high degree of structural and chemical complementarity. These results provide a molecular basis for the specific recognition of CD20 by Rituximab as well as valuable information for development of improved antibody drugs with better specificity and higher affinity.
Structural basis for recognition of CD20 by therapeutic antibody Rituximab.,Du J, Wang H, Zhong C, Peng B, Zhang M, Li B, Huo S, Guo Y, Ding J J Biol Chem. 2007 May 18;282(20):15073-80. Epub 2007 Mar 29. PMID:17395584[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kuijpers TW, Bende RJ, Baars PA, Grummels A, Derks IA, Dolman KM, Beaumont T, Tedder TF, van Noesel CJ, Eldering E, van Lier RA. CD20 deficiency in humans results in impaired T cell-independent antibody responses. J Clin Invest. 2010 Jan;120(1):214-22. doi: 10.1172/JCI40231. Epub 2009 Dec 21. PMID:20038800 doi:10.1172/JCI40231
- ↑ Du J, Wang H, Zhong C, Peng B, Zhang M, Li B, Huo S, Guo Y, Ding J. Structural basis for recognition of CD20 by therapeutic antibody Rituximab. J Biol Chem. 2007 May 18;282(20):15073-80. Epub 2007 Mar 29. PMID:17395584 doi:10.1074/jbc.M701654200
|
