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首页> 外文期刊>Journal of Molecular Biology >The Pierced Lasso Topology Leptin has a Bolt on Dynamic Domain Composed by the Disordered Loops I and III
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The Pierced Lasso Topology Leptin has a Bolt on Dynamic Domain Composed by the Disordered Loops I and III

机译：刺穿的套索拓扑瘦素具有由无序循环I和III组成的动态域上的螺栓

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摘要

Leptin is an important signaling hormone, mostly known for its role in energy expenditure and satiety. Furthermore, leptin plays a major role in other proteinopathies, such as cancer, marked hyperphagia, impaired immune function, and inflammation. In spite of its biological relevance in human health, there are no NMR resonance assignments of the human protein available, obscuring high-resolution characterization of the soluble protein and/or its conformational dynamics, suggested as being important for receptor interaction and biological activity. Here, we report the nearly complete backbone resonance assignments of human leptin. Chemical shift-based secondary structure prediction confirms that in solution leptin forms a four-helix bundle including a pierced lasso topology. The conformational dynamics, determined on several timescales, show that leptin is monomeric, has a rigid four-helix scaffold, and a dynamic domain, including a transiently formed helix. The dynamic domain is anchored to the helical scaffold by a secondary hydrophobic core, pinning down the long loops of leptin to the protein body, inducing motional restriction without a well-defined secondary or tertiary hydrogen bond stabilized structure. This dynamic region is well suited for and may be involved in functional allosteric dynamics upon receptor binding. (C) 2020 Elsevier Ltd. All rights reserved.
机译：瘦素是一个重要的信号激素，主要是以其能量消耗和饱腹感的作用。此外，瘦素起着其它蛋白病，如癌症，明显过盛，免疫功能受损和炎症中起主要作用。尽管对人体健康的生物相关性的，也有人类蛋白质没有NMR共振分配可用的，模糊的可溶性蛋白质和/或它的构象动力学的高分辨表征，建议作为受体的相互作用和生物活性具有重要意义。在这里，我们报告人瘦素的近乎完整的骨干共振分配。化学位移为基础的二级结构预测确认在溶液中瘦素形成四螺旋束，包括一个穿孔的套索拓扑。的构象动力学，在几个时间尺度来确定，表明瘦素是单体的，具有刚性的四螺旋支架，和一个动态域，包括一个瞬时形成的螺旋。动态域名通过二次疏水核锚定到支架螺旋，瘦素的长回路牵制到蛋白体，诱导运动限制没有明确定义的仲或叔氢键稳定结构。这种动态区域非常适合，并且可以在功能性变构动力学在受体结合有关。 （c）2020 elestvier有限公司保留所有权利。

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