Spatial structure of the dimeric transmembrane domain of the growth factor receptor ErbB2 presumably corresponding to the receptor active state.
Proper lateral dimerization of the transmembrane domains of receptor tyrosine kinases is required for biochemical signal transduction across the plasma membrane. The spatial structure of the dimeric transmembrane domain of the growth factor receptor ErbB2 embedded into lipid bicelles was obtained by solution NMR, followed by molecular dynamics relaxation in an explicit lipid bilayer. ErbB2 transmembrane segments associate in a right-handed alpha-helical bundle through the N-terminal tandem GG4-like motif Thr652-X3-Ser656-X3-Gly660, providing an explanation for the pathogenic power of some oncogenic mutations.
Bocharov
Eduard V
EV
Division of Structural Biology, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Ulitsa Miklukho-Maklaya 16/10, Moscow 117997, Russia. bon@nmr.ru
Mineev
Konstantin S
KS
Volynsky
Pavel E
PE
Ermolyuk
Yaroslav S
YS
Tkach
Elena N
EN
Sobol
Alexander G
AG
Chupin
Vladimir V
VV
Kirpichnikov
Michail P
MP
Efremov
Roman G
RG
Arseniev
Alexander S
AS
D020816:Amino Acid Motifs; D002462:Cell Membrane / Q000378:metabolism*; D019281:Dimerization; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008968:Molecular Conformation; D009154:Mutation; D011487:Protein Conformation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry*
D008051:Lipid Bilayers; D008055:Lipids; D020794:Receptor Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human