This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

3pp4

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Current revision

Epitope characterization and crystal structure of GA101 provide insights into the molecular basis for the type I / type II distinction of anti- CD20 antibodies

Structural highlights

3pp4 is a 3 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.6Å
Ligands:
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

CD20 is a cell surface marker of normal and malignant B cells. Rituximab, a monoclonal antibody targeting CD20, has improved treatment of malignant lymphomas. Therapeutic CD20 antibodies are classified as either type I or II based on different mechanisms of killing malignant B-cells. To reveal the molecular basis of this distinction, we fine mapped the epitopes recognized by both types. We also determined the first X-ray structure of a type II antibody by crystallizing the obinutuzumab (GA101) Fab fragment alone and in complex with a CD20 cyclopeptide. Despite recognizing an overlapping epitope, GA101 binds CD20 in a completely different orientation than type I antibodies. Moreover, the elbow angle of GA101 is almost 30 degrees wider than in type I antibodies potentially resulting in different spatial arrangements of two CD20 molecules bound to a single GA101 or rituximab molecule. By protein tomography different CD20 complexes were found associated with the two antibodies and confocal microscopy showed different membrane compartmentalization of these subpopulations of the cellular CD20 pool. Taken together, our findings offer a possible molecular explanation for the different cellular responses elicited by type I and II antibodies.

Epitope characterization and crystal structure of GA101 provide insights into the molecular basis for type I/II distinction of CD20 antibodies.,Niederfellner G, Lammens A, Mundigl O, Georges GJ, Schaefer W, Schwaiger M, Franke A, Wiechmann K, Jenewein S, Slootstra JW, Timmerman P, Brannstrom A, Lindstrom F, Mossner E, Umana P, Hopfner KP, Klein C Blood. 2011 Mar 28. PMID:21444918^[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
↑ Niederfellner G, Lammens A, Mundigl O, Georges GJ, Schaefer W, Schwaiger M, Franke A, Wiechmann K, Jenewein S, Slootstra JW, Timmerman P, Brannstrom A, Lindstrom F, Mossner E, Umana P, Hopfner KP, Klein C. Epitope characterization and crystal structure of GA101 provide insights into the molecular basis for type I/II distinction of CD20 antibodies. Blood. 2011 Mar 28. PMID:21444918 doi:10.1182/blood-2010-09-305847

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3pp4"

Categories: Homo sapiens | Large Structures | Mus musculus | Hopfner K-P | Lammens A

@@ Line 1: / Line 1: @@
 ==Epitope characterization and crystal structure of GA101 provide insights into the molecular basis for the type I / type II distinction of anti- CD20 antibodies==
-<StructureSection load='3pp4' size='340' side='right' caption='[[3pp4]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
+<StructureSection load='3pp4' size='340' side='right'caption='[[3pp4]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3pp4]] is a 3 chain structure with sequence from [http://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=3PP4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3PP4 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3pp4]] is a 3 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=3PP4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3PP4 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></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]] 1.6&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3pp3|3pp3]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3pp4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3pp4 OCA], [http://pdbe.org/3pp4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3pp4 RCSB], [http://www.ebi.ac.uk/pdbsum/3pp4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3pp4 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=3pp4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3pp4 OCA], [https://pdbe.org/3pp4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3pp4 RCSB], [https://www.ebi.ac.uk/pdbsum/3pp4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3pp4 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>
+[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 ==
-[[http://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.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 24: / Line 24: @@
 ==See Also==
 *[[Antibody 3D structures|Antibody 3D structures]]
+*[[Sandbox 20009|Sandbox 20009]]
+*[[3D structures of non-human antibody|3D structures of non-human antibody]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Lk3 transgenic mice]]
+[[Category: Homo sapiens]]
-[[Category: Hopfner, K P]]
+[[Category: Large Structures]]
-[[Category: Lammens, A]]
+[[Category: Mus musculus]]
-[[Category: Antibody antigen]]
+[[Category: Hopfner K-P]]
-[[Category: Antibody fab fragment ig-domain]]
+[[Category: Lammens A]]
-[[Category: Cd20]]
-[[Category: Cyclic peptide]]
-[[Category: Immune system]]

3pp4

From Proteopedia

Current revision

Epitope characterization and crystal structure of GA101 provide insights into the molecular basis for the type I / type II distinction of anti- CD20 antibodies

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox