Comparison of EGF receptor sequences as a guide to study the ligand binding site.
While murine and human EGF-receptor (EGF-R) bind mammalian EGF with high affinity their chicken counterpart has approximately 300 fold reduced binding affinity towards mammalian EGF. We now cloned and sequenced the extracellular ligand binding domain of murine EGF-R in order to define the amino-acids which comprise the binding site for EGF. Comparison of human, murine and chicken EGF-R allows the identification of amino acid substitutions which are conservative and would not affect EGF binding, substitutions which are responsible for the low affinity binding of EGF to chicken EGF-R and those responsible for the high affinity binding of EGF to mammalian EGF-R. This analysis will enable future design of point mutations in the EGF-R which will restore the high affinity binding for EFG typical of human or murine EGF-R.
Avivi
A
A
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
Lax
I
I
Ullrich
A
A
Schlessinger
J
J
Givol
D
D
Morse
B
B
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics*; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D012689:Sequence Homology, Nucleic Acid
D004815:Epidermal Growth Factor; D066246:ErbB Receptors