Structure of the Fab fragment of the anti-murine EGFR antibody 7A7 and exploration of its receptor binding site.
Artikel i vetenskaplig tidskrift, 2011
The EGF receptor is an important target of cancer immunotherapies. The 7A7 monoclonal antibody has been raised against the murine EGFR, but it cross-reacts with the human receptor. The results from experiments using immune-competent mice can therefore, in principle, be extrapolated to the corresponding scenario in humans. In this work we report the crystal structure of the 7A7 Fab at an effective resolution of 1.4Å. The antibody binding site comprises a deep pocket, located at the interface between the light and heavy chains, with major contributions from CDR loops H1, H2, H3 and L1. Binding experiments show that 7A7 recognizes a site on the EGFR extracellular domain that is not accessible in its most stable conformations, but that becomes exposed upon treatment with a tyrosine kinase inhibitor. This suggests a recognition mechanism similar to that proposed for mAb 806.
antagonists & inhibitors
Molecular
Receptor
Cross Reactions
immunology
Static Electricity
metabolism
Antibody
Animals
chemistry
X-Ray
metabolism
Antibodies
Binding Sites
Antigen-Antibody Complex
Crystallography
Protein Conformation
metabolism
Mice
Protein-Tyrosine Kinases
Models
chemistry
Amino Acid Sequence
Epidermal Growth Factor
Immunoglobulin Fab Fragments
Monoclonal
immunology
Författare
Ariel Talavera
Jenny Mackenzie
Greta Garrido
Rosmarie Friemann
Göteborgs universitet
Alejandro López-Requena
Ernesto Moreno
Ute Krengel
Publicerad i
Molecular immunology
1872-9142 (ISSN)
Vol. 48 Nummer/häfte 12-13 s. 1578-85Kategorisering
Ämneskategorier (SSIF 2011)
Strukturbiologi
Identifikatorer
DOI
10.1016/j.molimm.2011.03.016
PubMed
21592580