The β subunit determines the ligand binding properties of synaptic glycine receptors
The β subunit determines the ligand binding properties of synaptic glycine receptors
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DOI：
10.1016/j.neuron.2005.01.028
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发表时间：
2005-03-03
期刊：
影响因子：
16.2
通讯作者：
Laube, B
中科院分区：
文献类型：
--
作者：
Grudzinska, J;Schemm, R;Laube, B
抑制性甘氨酸受体（GlyRs）调节脊髓和其他脑区域中的运动协调和感觉信号处理。GlyR是由跨膜α和β亚基组成的五聚体蛋白。在这里，定点诱变结合同源性建模的基础上的乙酰胆碱结合蛋白的晶体结构，确定重组同源寡聚体α 1 β和异源寡聚体α 1 β GlyRs的关键配体结合残基。这揭示了位于相邻亚基界面上的两个高度保守的带相反电荷的残基对于激动剂结合至关重要。此外，发现P亚基决定异源寡聚GlyRs的配体结合特性。alp串联构建体的表达和代谢标记的GlyRs的亲和纯化证实了2 α 3 β的亚基化学计量学。由于β亚基锚定GlyRs在突触位点，我们的研究结果具有重要意义的生物合成，聚类和药理学的突触GlyRs。
Inhibitory glycine receptors (GlyRs) regulate motor coordination and sensory signal processing in spinal cord and other brain regions. GlyRs are pentameric proteins composed of membrane-spanning alpha and beta subunits. Here, site-directed mutagenesis combined with homology modeling based on the crystal structure of the acetylcholine binding protein identified key ligand binding residues of recombinant homooligomeric alpha1beta and heterooligomeric alpha1beta GlyRs. This disclosed two highly conserved, oppositely charged residues located on adjacent subunit interfaces as being crucial for agonist binding. In addition, the P subunit was found to determine the ligand binding properties of heterooligomeric GlyRs. Expression of an alp tandem construct and affinity purification of metabolically labeled GlyRs confirmed a subunit stoichionnetry of 2alpha3beta. Because the beta subunit anchors GlyRs at synaptic sites, our results have important implications for the biosynthesis, clustering, and pharmacology of synaptic GlyRs.