2OSL

Crystal structure of Rituximab Fab in complex with an epitope peptide

Summary for 2OSL

• Entry DOI: 10.2210/pdb2osl/pdb
• Descriptor: light chain of the Rituximab Fab fragment,light chain of the Rituximab Fab fragment, heavy chain of the Rituximab Fab fragment,heavy chain of the Rituximab Fab fragment, B-lymphocyte antigen CD20, ... (4 entities in total)
• Functional Keywords: fab-peptide complex, rituximab, chimeric antibody, immune system
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 6
• Total formula weight: 99328.43

Authors

Du, J.,Zhong, C.,Ding, J. (deposition date: 2007-02-06, release date: 2007-04-10, Last modification date: 2024-10-16)

Primary citation

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., 282:15073-15080, 2007

PubMed Abstract: 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.

PubMed: 17395584
DOI: 10.1074/jbc.M701654200

Experimental method

X-RAY DIFFRACTION (2.6 Å)