Solution structure of a new hypothalamic neuropeptide, human hypocretin-2/orexin-B
Solution structure of a new hypothalamic neuropeptide, human hypocretin-2/orexin-B
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DOI：
10.1046/j.1432-1327.1999.00911.x
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发表时间：
1999-12-01
期刊：
影响因子：
--
通讯作者：
Lee, W
中科院分区：
文献类型：
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作者：
Lee, LH;Bang, E;Lee, W
食欲素-A和食欲素-B（也称为hypocretin-1和hypocretin-2，分别）是一个单一的mRNA转录编码的下丘脑神经肽，它们刺激食物的摄入。我们利用二维核磁共振氢谱和动态模拟退火计算确定了人下丘脑泌素-2/食欲素-B的三维溶液结构。根据NOE、（3）J（HN α）偶合常数、氢-氘交换速率和化学位移指数，推测人下丘脑泌素-2/食欲素-B在水和30%三氟乙醇溶液中均由两个由短连接体连接的OL-螺旋组成。螺旋I的螺旋轴相对于螺旋II定向约60-80度。混合距离几何和模拟退火协议被用来生成一个合奏的30个结构，没有约束违反大于0.03纳米的距离和3度的角度。此外，人下丘脑泌素-2/食欲素-B与人神经肽Y共享相似的二级结构基序。这一结果为进一步研究人食欲素受体的配体-受体识别奠定了基础。
Orexin-A and orexin-B (also called hypocretin-1 and hypocretin-2, respectively) are novel hypothalamic neuropeptides encoded by a single mRNA transcript; they stimulate food intake. We have determined the three-dimensional solution structure of human hypocretin-2/orexin-B using two-dimensional H-1-NMR data and dynamical simulated annealing calculations. On the basis of NOEs, (3)J(HN alpha) coupling constants and hydrogen-deuterium exchange rates together with chemical shift indices, human hypocretin-2/orexin-B was deduced to consist of two ol-helices connected with a short linker in both H2O and 30% trifluoroethanol solutions. The helical axis of helix I is oriented about 60-80 degrees relative to helix II. Hybrid distance geometry and simulated-annealing protocols were used to generate an ensemble of 30 structures with no constraint violations greater than 0.03 nm for distances and 3 degrees for angles. In addition, human hypocretin-2/orexin-B shares a similar secondary-structural motif with human neuropeptide Y. This result can form the basis for further study on ligand-receptor recognition of human orexin receptors.