6vja

From Proteopedia

(Difference between revisions)

Current revision

Structure of CD20 in complex with rituximab Fab

6vja, resolution 3.30Å

Structural highlights

6vja is a 6 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	MS4A1, CD20 (HUMAN)
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

Publication Abstract from PubMed

Cluster of Differentiation 20 (CD20) is a B cell membrane protein that is targeted by monoclonal antibodies for the treatment of malignancies and auto-immune disorders, but whose structure and function are unknown. Rituximab (RTX) has been in clinical use for two decades, but how it activates complement to kill B cells remains poorly understood. We obtained a structure of CD20 in complex with RTX, revealing CD20 as a compact double-barrel dimer bound by two RTX antigen-binding fragments (Fabs), each of which engages a composite epitope and an extensive homotypic Fab:Fab interface. Our data suggest that RTX crosslinks CD20 into circular assemblies and lead to a structural model for complement recruitment. Our results further highlight the potential relevance of homotypic Fab:Fab interactions in targeting oligomeric cell-surface markers.

Structure of CD20 in complex with the therapeutic monoclonal antibody rituximab.,Rouge L, Chiang N, Steffek M, Kugel C, Croll TI, Tam C, Estevez A, Arthur CP, Koth CM, Ciferri C, Kraft E, Payandeh J, Nakamura G, Koerber JT, Rohou A Science. 2020 Feb 20. pii: science.aaz9356. doi: 10.1126/science.aaz9356. PMID:32079680^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ Rouge L, Chiang N, Steffek M, Kugel C, Croll TI, Tam C, Estevez A, Arthur CP, Koth CM, Ciferri C, Kraft E, Payandeh J, Nakamura G, Koerber JT, Rohou A. Structure of CD20 in complex with the therapeutic monoclonal antibody rituximab. Science. 2020 Feb 20. pii: science.aaz9356. doi: 10.1126/science.aaz9356. PMID:32079680 doi:http://dx.doi.org/10.1126/science.aaz9356

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6vja"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6vja is ON HOLD
+==Structure of CD20 in complex with rituximab Fab==
+<SX load='6vja' size='340' side='right' viewer='molstar' caption='[[6vja]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6vja]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VJA OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6VJA FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MS4A1, CD20 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6vja FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vja OCA], [http://pdbe.org/6vja PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6vja RCSB], [http://www.ebi.ac.uk/pdbsum/6vja PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6vja ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[[http://www.uniprot.org/uniprot/CD20_HUMAN CD20_HUMAN]] Defects in MS4A1 are the cause of immunodeficiency common variable type 5 (CVID5) [MIM:[http://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 ==
+[[http://www.uniprot.org/uniprot/CD20_HUMAN CD20_HUMAN]] This protein may be involved in the regulation of B-cell activation and proliferation.
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Cluster of Differentiation 20 (CD20) is a B cell membrane protein that is targeted by monoclonal antibodies for the treatment of malignancies and auto-immune disorders, but whose structure and function are unknown. Rituximab (RTX) has been in clinical use for two decades, but how it activates complement to kill B cells remains poorly understood. We obtained a structure of CD20 in complex with RTX, revealing CD20 as a compact double-barrel dimer bound by two RTX antigen-binding fragments (Fabs), each of which engages a composite epitope and an extensive homotypic Fab:Fab interface. Our data suggest that RTX crosslinks CD20 into circular assemblies and lead to a structural model for complement recruitment. Our results further highlight the potential relevance of homotypic Fab:Fab interactions in targeting oligomeric cell-surface markers.
-Authors:
+Structure of CD20 in complex with the therapeutic monoclonal antibody rituximab.,Rouge L, Chiang N, Steffek M, Kugel C, Croll TI, Tam C, Estevez A, Arthur CP, Koth CM, Ciferri C, Kraft E, Payandeh J, Nakamura G, Koerber JT, Rohou A Science. 2020 Feb 20. pii: science.aaz9356. doi: 10.1126/science.aaz9356. PMID:32079680<ref>PMID:32079680</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 6vja" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</SX>
+[[Category: Human]]
+[[Category: Large Structures]]
+[[Category: Croll, T I]]
+[[Category: Rohou, A]]
+[[Category: Antibody]]
+[[Category: Cd20]]
+[[Category: Immune system]]
+[[Category: Ms4a1]]
+[[Category: Rituximab]]
+[[Category: Therapeutic]]

6vja

From Proteopedia

Current revision

Structure of CD20 in complex with rituximab Fab

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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