Bocharov Eduard V, Mineev Konstantin S, Volynsky Pavel E, Ermolyuk Yaroslav S, Tkach Elena N, Sobol Alexander G, Chupin Vladimir V, Kirpichnikov Michail P, Efremov Roman G, Arseniev Alexander S
Division of Structural Biology, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Ulitsa Miklukho-Maklaya 16/10, Moscow 117997, Russia.
J Biol Chem. 2008 Mar 14;283(11):6950-6. doi: 10.1074/jbc.M709202200. Epub 2008 Jan 4.
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.
受体酪氨酸激酶跨膜结构域的适当侧向二聚化是跨质膜进行生化信号转导所必需的。通过溶液核磁共振获得了嵌入脂质双分子层中的生长因子受体ErbB2二聚体跨膜结构域的空间结构，随后在明确的脂质双层中进行分子动力学弛豫。ErbB2跨膜片段通过N端串联GG4样基序Thr652-X3-Ser656-X3-Gly660以右手α-螺旋束的形式缔合，这为一些致癌突变的致病能力提供了解释。
