Prediction of disease-related mutations affecting protein localization.
Prediction of disease-related mutations affecting protein localization.
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DOI：
10.1186/1471-2164-10-122
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发表时间：
2009-03-23
期刊：
影响因子：
4.4
通讯作者：
Vihinen M
中科院分区：
文献类型：
--
作者：
Laurila K;Vihinen M
真核细胞含有许多区室，这些区室具有不同的蛋白质组分。蛋白质通常通过充当靶向信号的短肽序列导向区室。转运到适当的区室允许蛋白质与其伴侣形成必要的相互作用，并参与生物网络，如信号传导和代谢途径。如果蛋白质没有被转运到正确的细胞内区室，则蛋白质进行的反应或携带的信息没有到达正确的位点，导致中心反应失活或信号级联失调，或者错误定位的活性蛋白质通过在错误的位置起作用而产生有害影响。人们已经开发了许多方法来以相当高的准确度预测蛋白质亚细胞定位。我们应用生物信息学方法研究已知疾病相关突变对蛋白质靶向和定位的影响，通过两种互补的预测方法分析了1,500多种蛋白质中的22,000多个错义突变。几百个假定的影响突变的定位进行了鉴定和统计学研究。虽然定位信号的改变是罕见的，但在分析疾病相关突变的后果时应考虑这些影响。
Eukaryotic cells contain numerous compartments, which have different protein constituents. Proteins are typically directed to compartments by short peptide sequences that act as targeting signals. Translocation to the proper compartment allows a protein to form the necessary interactions with its partners and take part in biological networks such as signalling and metabolic pathways. If a protein is not transported to the correct intracellular compartment either the reaction performed or information carried by the protein does not reach the proper site, causing either inactivation of central reactions or misregulation of signalling cascades, or the mislocalized active protein has harmful effects by acting in the wrong place. Numerous methods have been developed to predict protein subcellular localization with quite high accuracy. We applied bioinformatics methods to investigate the effects of known disease-related mutations on protein targeting and localization by analyzing over 22,000 missense mutations in more than 1,500 proteins with two complementary prediction approaches. Several hundred putative localization affecting mutations were identified and investigated statistically. Although alterations to localization signals are rare, these effects should be taken into account when analyzing the consequences of disease-related mutations.
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