Phylogenetic and In Silico Structural Analysis of the Parkinson Disease-Related Kinase PINK1
Phylogenetic and In Silico Structural Analysis of the Parkinson Disease-Related Kinase PINK1
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DOI：
10.1002/humu.21444
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发表时间：
2011-04-01
期刊：
影响因子：
3.9
通讯作者：
Perez-Tur, Jordi
中科院分区：
文献类型：
--
作者：
Cardona, Fernando;Vicente Sanchez-Mut, Jose;Perez-Tur, Jordi
帕金森病(PD)是第二常见的神经退行性疾病，以黑质多巴胺能神经元丢失为特征。PINK1基因突变被证明可导致隐性家族性帕金森病，目前被认为通过线粒体功能障碍和氧化损伤与该病有关。PINK1基因由8个外显子组成，编码一个普遍表达的581个氨基酸的蛋白，该蛋白含有一个N端的线粒体靶向结构域和一个丝氨酸/苏氨酸蛋白激酶。为了更好地理解PINK1和PD之间的关系，我们首先分析了该基因的进化史，表明其在进化中出现的时间较晚。此外，我们还模拟了PINK1的三维结构，发现了一些证据，有助于解释一些与PD相关的突变对该蛋白功能的影响。嗡嗡作响32：369-378,2011。(C)2011年Wiley-Liss，Inc.
Parkinson disease (PD) is the second most common neurodegenerative disorder and is characterized by the loss of dopaminergic neurons in the substantia nigra. Mutations in PINK1 were shown to cause recessive familial PD, and today are proposed to be associated with the disease via mitochondrial dysfunction and oxidative damage. The PINK1 gene comprises eight exons, which encode a ubiquitously expressed 581 amino acid protein that contains an N-terminal mitochondrial targeting domain and a serine/threonine protein kinase. To better understand the relationship between PINK1 and PD we have first analyzed the evolutionary history of the gene showing its late emergence in evolution. In addition, we have modeled the three-dimensional structure of PINK1 and found some evidences that help to explain the effect of some PD-related mutations in this protein's function. Hum Mutat 32: 369-378, 2011. (C) 2011 Wiley-Liss, Inc.