Solution structure of an M-1 conotoxin with a novel disulfide linkage
Solution structure of an M-1 conotoxin with a novel disulfide linkage
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DOI：
10.1111/j.1742-4658.2007.05795.x
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发表时间：
2007-05-01
期刊：
影响因子：
5.4
通讯作者：
Fang, Wei-Hai
中科院分区：
文献类型：
--
作者：
Du, Wei-Hong;Han, Yu-Hong;Fang, Wei-Hai
芋螺毒素的M-超家族具有典型的Cys框架（-CC-C-C-CC-），并且是在芋螺毒液中发现的八个主要超家族之一。根据位于最后一个Cys环（Cys 4和Cys 5之间）的残基数量，M-超家族家族可分为四个分支，即M-1、M-2、M-3和M-4。最近，两个M-1分支芋螺毒素（mr 3e和tx 3a）被报道在Cys 1和Cys 5、Cys 2和Cys 4以及Cys 3和Cys 6之间具有新的二硫键排列，这与在M-2和M-4分支中所看到的不同。在这里，我们报告的三维结构的mr 3e确定的2D H-1 NMR在水溶液中。根据NOE连接性得到的190个距离约束，以及6个phi二面角、3个氢键和3个二硫键约束，得到了该肽的20个收敛结构。骨架原子平均坐标的rmsd值为0.43 +/-0.19埃。虽然mr 3e具有与M-2和M-4芋螺毒素相同的Cys排列，但它采用独特的骨架构象，整个分子类似于“飞鸟”。因此，具有相同Cys框架的芋螺毒素可以采用不同的二硫键以产生更多样化的骨架支架。
The M-superfamily of conotoxins has a typical Cys framework (-CC-C-C-CC-), and is one of the eight major superfamilies found in the venom of the cone snail. Depending on the number of residues located in the last Cys loop (between Cys4 and Cys5), the M-superfamily family can be divided into four branches, namely M-1, -2, -3 and -4. Recently, two M-1 branch conotoxins (mr3e and tx3a) have been reported to possess a new disulfide bond arrangement between Cys1 and Cys5, Cys2 and Cys4, and Cys3 and Cys6, which is different from those seen in the M-2 and M-4 branches. Here we report the 3D structure of mr3e determined by 2D H-1 NMR in aqueous solution. Twenty converged structures of this peptide were obtained on the basis of 190 distance constraints obtained from NOE connectivities, as well as six phi dihedral angle, three hydrogen bond, and three disulfide bond constraints. The rmsd values about the averaged coordinates of the backbone atoms were 0.43 +/- 0.19 angstrom. Although mr3e has the same Cys arrangement as M-2 and M-4 conotoxins, it adopts a distinctive backbone conformation with the overall molecule resembling a 'flying bird'. Thus, different disulfide linkages may be employed by conotoxins with the same Cys framework to result in a more diversified backbone scaffold.