Membrane protein stability analyses by means of protein energy profiles in case of nephrogenic diabetes insipidus.
Membrane protein stability analyses by means of protein energy profiles in case of nephrogenic diabetes insipidus.
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DOI：
10.1155/2012/790281
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发表时间：
2012
影响因子：
--
通讯作者：
Labudde D
中科院分区：
文献类型：
--
作者：
Heinke F;Labudde D
尿崩症（DI）是一种罕见的内分泌遗传性疾病，发病率低，估计每25，000 - 30，000活产1例。这种疾病的特征是多尿和代偿性多饮。DI的各种潜在原因可能是中枢缺陷，其中没有功能性精氨酸加压素（AVP）从垂体释放，或者可能是肾脏缺陷的结果（肾源性DI，NDI）。NDI是一种尽管存在AVP但患者仍无法浓缩尿液的疾病。这种抗利尿激素调节肾脏中形成的原尿的水重吸收过程。它与肾脏中的2型受体（V2 R）结合，诱导cAMP驱动的级联反应，导致水通道蛋白-2水通道插入顶膜。V2 R和水通道蛋白-2基因的突变通常导致NDI。我们研究了一种结构模型的V2 R在其结合和未结合状态的蛋白质稳定性，使用一种新的蛋白质能量分布的方法。此外，这些技术被应用于野生型和选择突变的水通道蛋白-2。我们表明，我们的结果符合实验水ux分析，这证实了我们的理论方法的适用性等效问题。
Diabetes insipidus (DI) is a rare endocrine, inheritable disorder with low incidences in an estimated one per 25,000–30,000 live births. This disease is characterized by polyuria and compensatory polydypsia. The diverse underlying causes of DI can be central defects, in which no functional arginine vasopressin (AVP) is released from the pituitary or can be a result of defects in the kidney (nephrogenic DI, NDI). NDI is a disorder in which patients are unable to concentrate their urine despite the presence of AVP. This antidiuretic hormone regulates the process of water reabsorption from the prourine that is formed in the kidney. It binds to its type-2 receptor (V2R) in the kidney induces a cAMP-driven cascade, which leads to the insertion of aquaporin-2 water channels into the apical membrane. Mutations in the genes of V2R and aquaporin-2 often lead to NDI. We investigated a structure model of V2R in its bound and unbound state regarding protein stability using a novel protein energy profile approach. Furthermore, these techniques were applied to the wild-type and selected mutations of aquaporin-2. We show that our results correspond well to experimental water ux analysis, which confirms the applicability of our theoretical approach to equivalent problems.
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