Energetics of ErbB1 Transmembrane Domain Dimerization in Lipid Bilayers
Energetics of ErbB1 Transmembrane Domain Dimerization in Lipid Bilayers
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DOI：
10.1016/j.bpj.2009.03.004
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发表时间：
2009-06-03
影响因子：
3.4
通讯作者：
Hristova, Kalina
中科院分区：
文献类型：
--
作者：
Chen, Lirong;Merzlyakov, Mikhail;Hristova, Kalina
研究最广泛的受体酪氨酸激酶之一是EGFR/ErbB 1。虽然我们的知识ErbB 1激活的胞外结构域和配体的作用已经大大增加了解决结构域的基础上，跨膜信号转导的确切机制仍然未知。预期跨膜结构域在二聚化过程中发挥重要作用，但ErbB 1 TM结构域对二聚体稳定性的贡献尚不清楚，已发表的结果相互矛盾。我们通过显示ErbB 1 TM结构域在脂质双层中二聚化并通过计算其对稳定性的贡献为~ 2.5 kcal/mol来解决这一争议。稳定性计算采用了两种不同的基于Forster共振能量转移的方法，得到了相同的结果。ErbB 1 TM结构域对稳定性的贡献超过了受体酪氨酸激酶二聚化倾向的变化，其可以将正常信号传导过程转化为致病过程，因此可能对生物功能很重要。
One of the most extensively studied receptor tyrosine kinases is EGFR/ErbB1. Although our knowledge of the role of the extracellular domains and ligands in ErbB1 activation has increased dramatically based on solved domain structures, the exact mechanism of signal transduction across the membrane remains unknown. The transmembrane domains are expected to play an important role in the dimerization process, but the contribution of ErbB1 TM domain to dimer stability is not known, with published results contradicting one another. We address this controversy by showing that ErbB1 TM domain dimerizes in lipid bilayers and by calculating its contribution to stability as -2.5 kcal/mol. The stability calculations use two different methods based on Forster resonance energy transfer, which give the same result. The ErbB1 TM domain contribution to stability exceeds the change in receptor tyrosine kinases dimerization propensities that can convert normal signaling processes into pathogenic processes, and is thus likely important for biological function.