The A391E mutation enhances FGFR3 activation in the absence of ligand
The A391E mutation enhances FGFR3 activation in the absence of ligand
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DOI：
10.1016/j.bbamem.2011.04.007
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发表时间：
2011-08-01
影响因子：
3.4
通讯作者：
Hristova, Kalina
中科院分区：
文献类型：
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作者：
Chen, Fenghao;Degnin, Catherine;Hristova, Kalina
成纤维细胞生长因子受体3跨膜区A391 E突变导致颅骨发育异常据推测，突变谷氨酸稳定二聚体受体由于氢键和增强其配体非依赖性激活。我们先前在脂质双层中测试了这一假设，并表明突变使分离的跨膜结构域二聚体稳定了-1.3度kcal/mol。在这里，我们进一步测试的假设，通过研究的A391 E突变的全长成纤维细胞生长因子受体3在人胚肾293 T细胞在配体的情况下激活的影响。我们发现，该突变增强了受体的配体非依赖性激活倾向-1.7度kcal/mol。该值与膜中观察到的氢键强度一致，并支持上述假设。(C)2011爱思唯尔有限公司版权所有。
The A391E mutation in the transmembrane domain of fibroblast growth factor receptor 3 leads to aberrant development of the cranium. It has been hypothesized that the mutant glutamic acid stabilizes the dimeric receptor due to hydrogen bonding and enhances its ligand-independent activation. We previously tested this hypothesis in lipid bilayers and showed that the mutation stabilizes the isolated transmembrane domain dimer by -1.3 degrees kcal/mol. Here we further test the hypothesis, by investigating the effect of the A391E mutation on the activation of full-length fibroblast growth factor receptor 3 in Human Embryonic Kidney 293T cells in the absence of ligand. We find that the mutation enhances the ligand-independent activation propensity of the receptor by -1.7 degrees kcal/mol. This value is consistent with the observed strength of hydrogen bonds in membranes, and supports the above hypothesis. (C) 2011 Elsevier B.V. All rights reserved.