Deciphering the structural framework of glycine receptor anchoring by gephyrin
Deciphering the structural framework of glycine receptor anchoring by gephyrin
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DOI：
10.1038/sj.emboj.7601029
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发表时间：
2006-03-22
期刊：
影响因子：
11.4
通讯作者：
Schindelin, H
中科院分区：
文献类型：
--
作者：
Kim, EY;Schrader, N;Schindelin, H
甘氨酸是脊髓和脑干中的主要抑制性神经递质。桥卟啉是实现高浓度的甘氨酸受体（GlyR）在突触后膜，这是至关重要的有效的甘氨酸能信号转导所需的。桥蛋白和GlyR之间的相互作用涉及桥蛋白的E-结构域和位于GlyR β亚基的跨膜区段3和4之间的细胞质环。在这里，我们分别以2.4和2.7埃的分辨率呈现了具有和不具有GlyR β环的桥蛋白E结构域的晶体结构。GlyR β环以对称的“钥匙和锁”方式结合到邻近二聚体界面的口袋中的每个E结构域单体。体外结合和体内共定位测定之后的结构引导的诱变证明，由桥卟啉的Phe 330和GlyR β-环的Phe 398和Ile 400形成的疏水相互作用对于结合是至关重要的。
Glycine is the major inhibitory neurotransmitter in the spinal cord and brain stem. Gephyrin is required to achieve a high concentration of glycine receptors (GlyRs) in the postsynaptic membrane, which is crucial for efficient glycinergic signal transduction. The interaction between gephyrin and the GlyR involves the E-domain of gephyrin and a cytoplasmic loop located between transmembrane segments three and four of the GlyR beta subunit. Here, we present crystal structures of the gephyrin E-domain with and without the GlyR beta-loop at 2.4 and 2.7 angstrom resolutions, respectively. The GlyR beta-loop is bound in a symmetric 'key and lock' fashion to each E-domain monomer in a pocket adjacent to the dimer interface. Structure-guided mutagenesis followed by in vitro binding and in vivo colocalization assays demonstrate that a hydrophobic interaction formed by Phe 330 of gephyrin and Phe 398 and Ile 400 of the GlyR beta-loop is crucial for binding.