title: Interaction between ErbB-1 and ErbB-2 transmembrane domains in bilayer membranes.
abstract: The transmembrane domains of ErbB receptor tyrosine kinases are monotopic helical structures proposed to be capable of direct side-to-side contact with related receptors. Formation of the resulting homo- or hetero-oligomeric complexes is considered a key step in ligand-mediated signalling. ErbB-2, which has not been observed to form active homo-dimers in a ligand dependent manner, has been implicated as an important partner for formation of hetero-dimers with other ErbB receptors. Recent work has shown that the ErbB-2 transmembrane domain is capable of forming homo-oligomeric species in lipid bilayers, while a similar domain from ErbB-1 appears to have a lesser tendency to such interactions. Here, 2H nuclear magnetic resonance was used to investigate the role of the ErbB-2 transmembrane domain in hetero-oligomerisation with that of ErbB-1. At low total concentrations of peptide in the membrane, ErbB-2 transmembrane domains were found to decrease the mobility of corresponding ErbB-1 domains. The results are consistent with the existence of direct transmembrane domain involvement in hetero-oligomer formation within the ErbB receptor family.
authors.affiliation: Department of Biochemistry, University of Western Ontario, London, ON, Canada. sjsharpe@uwo.ca
authors.forename: Simon
authors.initials: S
authors.lastname: Sharpe
authors.forename: Kathryn R
authors.initials: KR
authors.lastname: Barber
authors.forename: Chris W M
authors.initials: CW
authors.lastname: Grant
mesh_terms: D000595:Amino Acid Sequence; D003903:Deuterium; D019281:Dimerization; D066246:ErbB Receptors / Q000737:chemistry*; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry*
chemical_list: D003903:Deuterium; D066246:ErbB Receptors; D008051:Lipid Bilayers; D010446:Peptide Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases