Crystal structures of β-neurexin 1 and β-neurexin 2 ectodomains and dynamics of splice insertion sequence 4
Crystal structures of β-neurexin 1 and β-neurexin 2 ectodomains and dynamics of splice insertion sequence 4
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DOI：
10.1016/j.str.2007.12.024
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发表时间：
2008-03-01
期刊：
影响因子：
5.7
通讯作者：
Shapiro, Lawrence
中科院分区：
文献类型：
--
作者：
Koehnke, Jesko;Jin, Xiangshu;Shapiro, Lawrence
突触前神经毒素（NRXs）与突触后神经配素（NL）结合形成桥接神经突触的Ca 2+依赖性复合物。β-NRX通过其LNS结构域结合NL，其含有单一可变剪接位点（剪接位点4），产生两种同种型：+4和δ。我们目前的δ异构体的LNS域从β-NRX 1和β-NRX 2的晶体结构，在Ca 2+离子的存在下结晶。β-NRX 2结构中的Ca 2+结合位点是无序的，但1.7埃的β-NRX 1结构显示了一个单一的Ca 2+离子，类似于剪接插入位点的12埃，其中一个配位配体由相邻的β-NRX 1分子中的谷氨酸提供。对β-NRX 1 +4的NMR研究表明，插入序列是非结构化的，并且在与NL的复合物中至少保持部分无序。这些结果提高了β-NRX插入序列4可能独立于神经配蛋白结合发挥作用的可能性。
Presynaptic neurexins (NRXs) bind to postsynaptic neuroligins (NLs) to form Ca2+-dependent complexes that bridge neural synapses. beta-NRXs bind NLs through their LNS domains, which contain a single site of alternative splicing (splice site 4) giving rise to two isoforms: +4 and Delta. We present crystal structures of the Delta isoforms of the LNS domains from beta-NRX1 and beta-NRX2, crystallized in the presence of Ca2+ ions. The Ca2+ -binding site is disordered in the beta-NRX2 structure, but the 1.7 angstrom beta-NRX1 structure revealsasingle Ca2+ ion, similar to 12 angstrom from the splice insertion site, with one coordinating ligand donated by a glutamic acid from an adjacent beta-NRX1 molecule. NMR studies of beta-NRX1+4 show that the insertion sequence is unstructured, and remains at least partially disordered in complex with NL. These results raise the possibility that beta-NRX insertion sequence 4 may function in roles independent of neuroligin binding.