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

Molecular immunology

1872-9142 (ISSN)

Vol. 48 12-13 1578-85

Ämneskategorier

Strukturbiologi

DOI

10.1016/j.molimm.2011.03.016

PubMed

21592580