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Structural mechanism of the antigen recognition by the L1 cell adhesion molecule antibody A10‐A3
Author(s) -
Wei Chun Hua,
Lee Eung Suk,
Jeon Jeong Yi,
Heo Yong-Seok,
Kim Seung Jun,
Jeon Young Ho,
Kim Kyung Hyun,
Hong Hyo Jeong,
Ryu Seong Eon
Publication year - 2011
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2010.11.028
Subject(s) - epitope , l1 , antibody , antigen , chemistry , mechanism (biology) , conformational epitope , microbiology and biotechnology , angstrom , biology , biochemistry , crystallography , immunology , gene , philosophy , epistemology
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.