Prediction of potential GPI-modification sites in proprotein sequences

Prediction of potential GPI-modification sites in proprotein sequences
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DOI:
10.1006/jmbi.1999.3069
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发表时间:
1999-09-24
影响因子:
5.6
通讯作者:
Eisenhaber, F
Eisenhaber, F
中科院分区:
生物学2区
文献类型:
--
作者:
Eisenhaber, B;Bork, P;Eisenhaber, F

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糖基磷脂酰肌醇(GPI)脂质锚定是一种常见的翻译后修饰,主要来自细胞外真核蛋白。GPI部分与多肽的羧基末端(ω-位点)的连接在C-末端前肽的蛋白水解切割之后进行。这是第一次,一种新的预测技术定位潜在的GPI修饰位点的前体序列已被应用于大规模的蛋白质序列数据库搜索。复合预测功能(与单独的参数化后生动物和原生动物蛋白质)包括评估两个氨基酸类型的偏好,在序列位置附近的假定的ω-网站,以及一致性与一般的物理性质编码的基序序列内的多残基相关性的条款。后一个术语在拒绝考虑不适当的序列方面特别成功。该算法已被验证与自一致性和两个刀切测试的学习集的完全注释的序列从SWISS-PROT数据库,以及与一个新创建的数据库“大Pi”(超过300 GPI基序突变从原始文献来源提取)。预测GPI序列基序突变效应的准确率在83%以上。SWISS-PROT和SPTrEMBL中未注释的潜在前体蛋白的列表在WWW页面http://www.embl-heidelberg.de/beisenha/gpi/gpi_prediction.html上提供。该算法已在原型软件“big-Pi predictor”中实现,该软件可用作基因组注释和靶选择工具。(C)北京:科学出版社.
Glycosylphosphatidylinositol (GPI) lipid anchoring is a common posttranslational modification known mainly from extracellular eukaryotic proteins. Attachment of the GPI moiety to the carboxyl terminus (omega-site) of the polypeptide follows after proteolytic cleavage of a C-terminal propeptide. For the first time, a new prediction technique locating potential GPI-modification sites in precursor sequences has been applied for large-scale protein sequence database searches. The composite prediction function (with separate parametrisation for metazoan and protozoan proteins) consists of terms evaluating both amino acid type preferences at sequence positions near a supposed omega-site as well as the concordance with general physical properties encoded in multi-residue correlation within the motif sequence. The latter terms are especially successful in rejecting non-appropriate sequences from consideration. The algorithm has been validated with a self-consistency and two jack-knife tests for the learning set of fully annotated sequences from the SWISS-PROT database as well as with a newly created database "big-Pi" (more than 300 GPI-motif mutations extracted from original literature sources). The accuracy of predicting the effect of mutations in the GPI sequence motif was above 83 %. Lists of potential precursor proteins which are non-annotated in SWISS-PROT and SPTrEMBL are presented on the WWW-page http://www.embl-heidelberg.de/beisenha/gpi/gpi_prediction.html The algorithm has been implemented in the prototype software "big-Pi predictor" which may find application as a genome annotation and target selection tool. (C) 1999 Academic Press.