Kawasaki Takashi, Saka Takahiro, Mine Shouhei, Mizohata Eiichi, Inoue Tsuyoshi, Matsumura Hiroyoshi, Sato Takaaki
Health Research Institute, National Institute of Advanced Industrial Science and Technology, 3-11-46 Nakoji, Amagasaki, Hyogo 661-0974, Japan.
Department of Applied Chemistry, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
FEBS Lett. 2015 Apr 28;589(10):1136-42. doi: 10.1016/j.febslet.2015.03.025. Epub 2015 Mar 31.
We previously observed highly rapid and robust response of murine olfactory receptor S6 (mOR-S6) with chimeric Gα15_olf, compared to Gα15. To identify residues responsible for this difference in response, mutations of the cytosolic helix 8 were analyzed in a heterologous functional expression system. The N-terminal hydrophobic core between helix 8 and TM1-2 of mOR-S6 is important for activation of both Gα15_olf and Gα15. Point mutation of a helix 8 N-terminal acidic residue eliminated the differences in response dynamics via Gα. This result suggests that an N-terminal acidic residue of helix 8 is responsible for rapid response via Gα15_olf.
我们之前观察到，与Gα15相比，嵌合Gα15_olf的小鼠嗅觉受体S6（mOR-S6）具有高度快速且强烈的反应。为了确定导致这种反应差异的残基，在异源功能表达系统中分析了胞质螺旋8的突变。mOR-S6螺旋8与跨膜结构域1-2之间的N端疏水核心对于Gα15_olf和Gα15的激活都很重要。螺旋8 N端酸性残基的点突变消除了通过Gα的反应动力学差异。这一结果表明，螺旋8的N端酸性残基负责通过Gα15_olf的快速反应。
