Interaction between ErbB‐1 and ErbB‐2 transmembrane domains in bilayer membranes

FEBS Letters

Grant, Chris W.M.¹  Barber, Kathryn R.¹  Sharpe, Simon¹ 

[1] Department of Biochemistry, University of Western Ontario, London, ON, Canada N6A 5C1

关键词: Deuterium nuclear magnetic resonance;    Peptide;    Model membrane;    Signal transduction;    ErbB-2;    ErbB-1;    Epidermal growth factor;    Dimer;    ErbB-2;    human class I receptor tyrosine kinase also known as HER2 or c-erbB-2 (neu in the rat);    ErbB-2TM;    a 50-residue expressed transmembrane peptide containing Gly648 to Met691 of ErbB-2 plus an N-terminal hexa-His tag;    EGF;    epidermal growth factor;    ErbB-1;    human EGF receptor;    ErbB-1TM;    a 38-residue expressed transmembrane peptide containing Pro620 to Arg651 of ErbB-1 plus an N-terminal hexa-His tag;    POPC;    1-palmitoyl-2-oleoyl-3-sn-phosphatidylcholine;    FACT;    formic acid/acetic acid/chloroform/trifluoroethanol (1:1:2:1 ratio by volume);   

DOI  :  10.1016/S0014-5793(02)02716-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown