title: Structural mechanism of the antigen recognition by the L1 cell adhesion molecule antibody A10-A3.
abstract: The L1CAM antibody A10-A3 efficiently reduces tumor growth in a nude mouse model. Here, we describe the crystal structure of the Fab fragment of A10-A3 determined at 2.0 angstrom resolution. The A10-A3 antibody H3 loop reveals a characteristic arrangement of exposed aromatic residues that may play an important role in antigen binding. A structure model of the complex between L1CAM Ig1-4 and A10-A3 Fab indicates that the Fab binds to three small loops outside Ig1 and a residue between Ig1 and Ig2, consistent with an epitope mapping result. The data presented here should contribute to the design of high-affinity antibody for therapeutic purposes as well as to the understanding of neural cell remodeling and cancer progression mechanism mediated by L1CAM.
authors.affiliation: Department of Bio-engineering, Hanyang University, Seoul, Republic of Korea.
authors.forename: Chun Hua
authors.initials: CH
authors.lastname: Wei
authors.forename: Eung Suk
authors.initials: ES
authors.lastname: Lee
authors.forename: Jeong Yi
authors.initials: JY
authors.lastname: Jeon
authors.forename: Yong-Seok
authors.initials: YS
authors.lastname: Heo
authors.forename: Seung Jun
authors.initials: SJ
authors.lastname: Kim
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Jeon
authors.forename: Kyung Hyun
authors.initials: KH
authors.lastname: Kim
authors.forename: Hyo Jeong
authors.initials: HJ
authors.lastname: Hong
authors.forename: Seong Eon
authors.initials: SE
authors.lastname: Ryu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D000936:Antigen-Antibody Complex / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D000941:Antigens / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D001665:Binding Sites; D003460:Crystallization; D018604:Epitope Mapping; D000939:Epitopes / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D039842:Neural Cell Adhesion Molecule L1 / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D014961:X-Ray Diffraction
chemical_list: D000906:Antibodies; D000936:Antigen-Antibody Complex; D000941:Antigens; D000939:Epitopes; D007140:Immunoglobulin Fab Fragments; D039842:Neural Cell Adhesion Molecule L1