title: Structural basis for recognition of CD20 by therapeutic antibody Rituximab.
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.
authors: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
authors: Jiamu
authors: J
authors: Du
authors: Hao
authors: H
authors: Wang
authors: Chen
authors: C
authors: Zhong
authors: Baozhen
authors: B
authors: Peng
authors: Meilan
authors: M
authors: Zhang
authors: Bohua
authors: B
authors: Li
authors: Sheng
authors: S
authors: Huo
authors: Yajun
authors: Y
authors: Guo
authors: Jianping
authors: J
authors: Ding
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000276:immunology; D058846:Antibodies, Monoclonal, Murine-Derived; D000915:Antibody Affinity; D000936:Antigen-Antibody Complex / Q000737:chemistry* / Q000276:immunology; D000937:Antigen-Antibody Reactions; D018951:Antigens, CD20 / Q000737:chemistry* / Q000276:immunology; D001666:Binding Sites, Antibody; D000939:Epitopes / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D006860:Hydrogen Bonding; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry* / Q000276:immunology; D020836:Protein Structure, Quaternary; D000069283:Rituximab; D013329:Structure-Activity Relationship
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000936:Antigen-Antibody Complex; D018951:Antigens, CD20; D000939:Epitopes; D007140:Immunoglobulin Fab Fragments; D000069283:Rituximab