3pp3: Difference between revisions
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==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='3pp3' size='340' side='right'caption='[[3pp3]], [[Resolution|resolution]] 2.51Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3pp3]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PP3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3PP3 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.508Å</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=3pp3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3pp3 OCA], [https://pdbe.org/3pp3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3pp3 RCSB], [https://www.ebi.ac.uk/pdbsum/3pp3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3pp3 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:21444918</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3pp3" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Antibody|Antibody]] | *[[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: Large Structures]] | |||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Hopfner | [[Category: Hopfner K-P]] | ||
[[Category: Lammens | [[Category: Lammens A]] | ||
Latest revision as of 12:58, 6 September 2023
Epitope characterization and crystal structure of GA101 provide insights into the molecular basis for the type I / type II distinction of anti- CD20 antibodiesEpitope 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
Publication Abstract from PubMedCD20 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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