Proteome-wide classification and identification of mammalian-type GPCRs by binary topology pattern
Proteome-wide classification and identification of mammalian-type GPCRs by binary topology pattern
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DOI：
10.1016/j.compbiolchem.2003.11.003
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发表时间：
2004-02-01
影响因子：
3.1
通讯作者：
Shimizu, J
中科院分区：
文献类型：
--
作者：
Inoue, Y;Ikeda, M;Shimizu, J
G蛋白偶联受体（gpcr）是一个庞大的真核蛋白家族，由于其高度分化，序列几乎没有相似性，因此很难通过同源性搜索和结构域检测来全面检测和功能鉴定。跨膜（TM）拓扑模式分析已被用于对TM蛋白进行分类，并且这种模式在功能相似的gpcr中是保守的。在此，我们建立了一种用于GPCR分类和鉴定的逐步二元拓扑模式（BTP）方法，并使用它对10种不同真核生物物种的哺乳动物型GPCR基因组进行了鉴定和分类。通过分配二进制环路阈值长度为“0”（短环路）或“1”（长环路），得到每个功能类或组的二进制拓扑模式。BTP方法的GPCR分类能力在类水平上（基于GPCRDB分类方案的A、B、C、frizzed /Smoothened、Non-GPCR）对GPCR功能进行分类的准确率很高，对许多类的分类准确率达到100%。在官能团水平上也保持了足够高的准确度，在15个官能团上达到0.945。利用BTP方法对10个真核生物基因组（智人、肌肉鼠、红毛鼠、肠芽胞杆菌、拟南拟南虫、黑腹拟南虫、冈比亚拟南虫、秀丽隐门线虫、恶性疟原虫、葡萄球菌）进行蛋白质组级哺乳动物型GPCR搜索，结果显示，与典型BLAST搜索相比，非哺乳动物基因组的分类/鉴定率更高，后者的非GPCR序列被分类率更高。这种逐步BTP方法将被证明对广泛物种基因组中gpcr的鉴定和功能分类是有用的。(C) 2003 Elsevier Ltd.版权所有。
G protein-coupled receptors (GPCRs), a large eukaryotic protein family, have proved difficult to comprehensively detect and functionally identify by homology searches and domain detection, because they are highly divergent and their sequences share strikingly little similarity. Transmembrane (TM) topology pattern analysis has been used to classify TM proteins, and such patterns are conserved within GPCRs of similar function. Here, we developed a stepwise binary topology pattern (BTP) method for GPCR classification and identification and used it to identify and classify mammalian-type GPCRs in the genomes of 10 different eukaryotic species. A binary topology pattern was obtained for each functional class or group by assigning binary loop threshold lengths of '0' (short loop) or '1' (long loop). The GPCR-classification ability of the BTP method had quite high accuracies for classifying GPCR functions at the class level (Classes A, B, C, Frizzled/Smoothened, Non-GPCR, based on the GPCRDB classification scheme), with many classes being classified with 100% accuracy. Sufficiently high accuracies were also maintained at the functional group level, 0.945 over 15 functional groups. Proteome-wide mammalian-type GPCR searches in 10 eukaryotic genomes (H. sapiens, M. musculus, F rubripes, C. intestinalis, A. thaliana, D. melanogaster, A. gambiae, C. elegans, P falciparum, S. cerevisiae) using the BTP method showed much higher classification/identification in non-mammalian genomes than typical BLAST searches, in which a higher number of sequences were classified as Non-GPCR. This stepwise BTP method should prove useful for the identification and functional classification of GPCRs from the genomes of a wide range of species. (C) 2003 Elsevier Ltd. All rights reserved.