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.
Copyright © 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Amino Acid Sequence
-
Animals
-
Antibodies / chemistry
-
Antibodies / immunology*
-
Antibodies / metabolism
-
Antigen-Antibody Complex / chemistry
-
Antigen-Antibody Complex / immunology*
-
Antigen-Antibody Complex / metabolism
-
Antigens / chemistry
-
Antigens / immunology*
-
Antigens / metabolism
-
Binding Sites
-
Crystallization
-
Epitope Mapping
-
Epitopes / chemistry
-
Epitopes / immunology
-
Epitopes / metabolism
-
HEK293 Cells
-
Humans
-
Immunoglobulin Fab Fragments / chemistry
-
Immunoglobulin Fab Fragments / immunology
-
Immunoglobulin Fab Fragments / metabolism
-
Mice
-
Models, Molecular
-
Neural Cell Adhesion Molecule L1 / chemistry
-
Neural Cell Adhesion Molecule L1 / immunology*
-
Neural Cell Adhesion Molecule L1 / metabolism
-
Protein Binding
-
Protein Conformation
-
Protein Structure, Tertiary
-
X-Ray Diffraction
Substances
-
Antibodies
-
Antigen-Antibody Complex
-
Antigens
-
Epitopes
-
Immunoglobulin Fab Fragments
-
Neural Cell Adhesion Molecule L1