title: Comparison of proto-oncogenic and mutant forms of the transmembrane region of the Neu receptor in TFE.
abstract: A single mutation within the transmembrane region of the Neu receptor (Val664-->Glu) is known to enhance tyrosine kinase activity, by promoting receptor dimerization. In order to gain insight into potential structural changes that arise as a result of the mutation, peptides corresponding to the complete transmembrane domain of proto-oncogenic and mutant forms of Neu have been studied by 1H nuclear magnetic resonance in the solvent trifluoroethanol (TFE). The chemical shifts are similar for both forms of the peptide, with the exception of amide residues close to the mutation site. Both peptides adopt a helical conformation, with a distinct bend one turn downstream of the mutation site. This deformation gives rise to several nuclear Overhauser effects, the majority of which were detected in both peptides, that are atypical for a straight canonical alpha-helix. Our data in this solvent do not support a conformational change in the transmembrane domain of monomeric Neu as a result of the mutation. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis indicates that proto-oncogenic Neu peptides have a higher propensity to oligomerize in the solvent TFE than the Glu664 oncogenic form.
authors.affiliation: Department of Chemistry and Biochemistry, University of Guelph, Guelph, ON, Canada , N1G 2W1.
authors.forename: R Scott
authors.initials: RS
authors.lastname: Houliston
authors.forename: Robert S
authors.initials: RS
authors.lastname: Hodges
authors.forename: Frances J
authors.initials: FJ
authors.lastname: Sharom
authors.forename: James H
authors.initials: JH
authors.lastname: Davis
mesh_terms: D019943:Amino Acid Substitution; D004591:Electrophoresis, Polyacrylamide Gel; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D010446:Peptide Fragments / Q000737:chemistry*; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry* / Q000235:genetics; D014270:Trifluoroethanol / Q000737:chemistry*
chemical_list: D010446:Peptide Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases; D014270:Trifluoroethanol