The NMDA receptor NR1 C1 region bound to calmodulin: Structural insights into functional differences between homologous domains
The NMDA receptor NR1 C1 region bound to calmodulin: Structural insights into functional differences between homologous domains
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DOI：
10.1016/j.str.2007.10.012
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发表时间：
2007-12-01
期刊：
影响因子：
5.7
通讯作者：
Shea, Madeline A.
中科院分区：
文献类型：
--
作者：
Ataman, Zeynep Akyol;Gakhar, Lokesh;Shea, Madeline A.
钙调素（CaM）通过与NR 1亚基的CO和C1区域紧密结合来调节四聚体N-甲基-D-天冬氨酸受体（NMDAR）。一种晶体结构（2 HQW; 1.96埃）的钙饱和的钙调素结合到NR 1C 1（肽跨度875-898）表明，NR 1 S890，其磷酸化调节膜定位，是溶剂保护，而内质网保留基序是溶剂暴露。NR 1 F880填充CaM C结构域口袋，而T886最接近N结构域口袋。这种1-7模式与CaM-MARCKS复合物中的模式最相似。钙调素-配体环绕构象的比较确定了钙调素C-结构域残基（FLMMC），接触所有配体一致的核心四分体。一个相同的四分体的N-结构域残基（FLMMN）与配体的接触可变集。这种CaM-NR 1C 1结构为设计突变体以测试CaM在NR 1运输中的作用以及深入了解同源CaM结构域如何在分子识别中具有不同的作用提供了基础。
Calmodulin (CaM) regulates tetrameric N-methyl-D-aspartate receptors (NMDARs) by binding tightly to the CO and C1 regions of its NR1 subunit. A crystal structure (2HQW; 1.96 angstrom) of calcium-saturated CaM bound to NR1C1 (peptide spanning 875-898) showed that NR1 S890, whose phosphorylation regulates membrane localization, was solvent protected, whereas the endoplasmic reticulum retention motif was solvent exposed. NR1 F880 filled the CaM C-domain pocket, whereas T886 was closest to the N-domain pocket. This 1-7 pattern was most similar to that in the CaM-MARCKS complex. Comparison of CaM-ligand wraparound conformations identified a core tetrad of CaM C-domain residues (FLMMC) that contacted all ligands consistently. An identical tetrad of N-domain residues (FLMMN) made variable sets of contacts with ligands. This CaM-NR1C1 structure provides a foundation for designing mutants to test the role of CaM in NR1 trafficking as well as insights into how the homologous CaM domains have different roles in molecular recognition.