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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.
AuthorsChun Hua Wei, Eung Suk Lee, Jeong Yi Jeon, Yong-Seok Heo, Seung Jun Kim, Young Ho Jeon, Kyung Hyun Kim, Hyo Jeong Hong, Seong Eon Ryu
JournalFEBS letters (FEBS Lett) Vol. 585 Issue 1 Pg. 153-8 (Jan 03 2011) ISSN: 1873-3468 [Electronic] England
PMID21094640 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Chemical References
  • Antibodies
  • Antigen-Antibody Complex
  • Antigens
  • Epitopes
  • Immunoglobulin Fab Fragments
  • Neural Cell Adhesion Molecule L1
Topics
  • Amino Acid Sequence
  • Animals
  • Antibodies (chemistry, immunology, metabolism)
  • Antigen-Antibody Complex (chemistry, immunology, metabolism)
  • Antigens (chemistry, immunology, metabolism)
  • Binding Sites
  • Crystallization
  • Epitope Mapping
  • Epitopes (chemistry, immunology, metabolism)
  • HEK293 Cells
  • Humans
  • Immunoglobulin Fab Fragments (chemistry, immunology, metabolism)
  • Mice
  • Models, Molecular
  • Neural Cell Adhesion Molecule L1 (chemistry, immunology, metabolism)
  • Protein Binding
  • Protein Conformation
  • Protein Structure, Tertiary
  • X-Ray Diffraction

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