Towards complete sets of farnesylated and geranylgeranylated proteins.
Towards complete sets of farnesylated and geranylgeranylated proteins.
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DOI：
10.1371/journal.pcbi.0030066
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发表时间：
2007-04-06
影响因子：
4.3
通讯作者：
Eisenhaber F
中科院分区：
文献类型：
--
作者：
Maurer-Stroh S;Koranda M;Benetka W;Schneider G;Sirota FL;Eisenhaber F
三种不同的戊烯基转移酶将异戊二烯基锚连接到底物蛋白的C-末端基序上。这些脂质锚在许多途径中起到膜附着或蛋白质-蛋白质相互作用的作用。尽管临床上有耐受性良好的选择性戊烯基转移酶抑制剂，但其作用模式尚不清楚，因为各种戊烯基转移酶的已知底物是不完整的。预基化预测套件(PREPS)已被应用于对预烯基化蛋白质的大规模预测。为了确定实验验证的目标的优先顺序，我们根据蛋白质家族中预烯基化基序的进化保守估计的功能重要性对预测进行了排名。预测的排序列表可以作为PRENbase(http://mendel.imp.univie.ac.at/sat/PrePS/PRENbase)访问，并且可以查询验证状态、修饰酶的类型(锚定类型)和分类分布。我们的结果突出了一大组植物金属结合伴侣以及几个新预测的参与泛素介导的蛋白质降解的蛋白质，丰富了已知的预烯基化蛋白质的功能谱系。此外，我们在Mimi病毒中发现了两种可能的前烯基化蛋白。Human PRENbase部分提供了预测的先烯基化人类蛋白的完整列表-例如，不能成为香叶基香叶基转移酶1底物的法尼基转移酶靶标的列表，因此特别受癌症和抗寄生虫治疗中使用的法尼基转移酶抑制剂(FTI)的影响。我们报告了直接的实验证据，证实了人类蛋白质Prickle1，Prickle2，含有BRO1结构域的FLJ32421(称为BROFTI)和Rab28(短异构体)作为唯一的法尼基转移酶靶标的预测。我们介绍了PRENbase，这是一个大规模预测蛋白质预烯基化底物的数据库，根据基序的进化保守进行排序。具有进化保守修饰位点的靶标的选择性法尼化提供了实验证据。各种细胞功能需要蛋白质可逆膜定位。这通常是通过将脂类附着到相应的蛋白质上，从而将它们锚定在膜上来促进的。例如，戊烯基脂锚基的添加(戊烯基化)是由蛋白质序列中的一个基序指导的，可以使用最近开发的方法预测。我们描述了所有已知蛋白质中蛋白质预烯基化的预测。带注释的结果可以在一个在线数据库PRENbase上获得。假设来自不同物种的相关蛋白质中存在一个预烯基化序列基序(进化保守)，与脂锚的功能重要性有关，本文对预测进行了排名。我们提供了实验证据，表明高排名的人类蛋白质预计会受到抗癌药物抑制早烯基化的影响。
Three different prenyltransferases attach isoprenyl anchors to C-terminal motifs in substrate proteins. These lipid anchors serve for membrane attachment or protein–protein interactions in many pathways. Although well-tolerated selective prenyltransferase inhibitors are clinically available, their mode of action remains unclear since the known substrate sets of the various prenyltransferases are incomplete. The Prenylation Prediction Suite (PrePS) has been applied for large-scale predictions of prenylated proteins. To prioritize targets for experimental verification, we rank the predictions by their functional importance estimated by evolutionary conservation of the prenylation motifs within protein families. The ranked lists of predictions are accessible as PRENbase (http://mendel.imp.univie.ac.at/sat/PrePS/PRENbase) and can be queried for verification status, type of modifying enzymes (anchor type), and taxonomic distribution. Our results highlight a large group of plant metal-binding chaperones as well as several newly predicted proteins involved in ubiquitin-mediated protein degradation, enriching the known functional repertoire of prenylated proteins. Furthermore, we identify two possibly prenylated proteins in Mimivirus. The section HumanPRENbase provides complete lists of predicted prenylated human proteins—for example, the list of farnesyltransferase targets that cannot become substrates of geranylgeranyltransferase 1 and, therefore, are especially affected by farnesyltransferase inhibitors (FTIs) used in cancer and anti-parasite therapy. We report direct experimental evidence verifying the prediction of the human proteins Prickle1, Prickle2, the BRO1 domain–containing FLJ32421 (termed BROFTI), and Rab28 (short isoform) as exclusive farnesyltransferase targets. We introduce PRENbase, a database of large-scale predictions of protein prenylation substrates ranked by evolutionary conservation of the motif. Experimental evidence is presented for the selective farnesylation of targets with an evolutionary conserved modification site. Various cellular functions require reversible membrane localization of proteins. This is often facilitated by attaching lipids to the respective proteins, thus anchoring them to the membrane. For example, addition of prenyl lipid anchors (prenylation) is directed by a motif in the protein sequence that can be predicted using a recently developed method. We describe the prediction of protein prenylation in all currently known proteins. The annotated results are available as an online database: PRENbase. A ranking of the predictions is introduced, assuming that existence of a prenylation sequence motif in related proteins from different species (evolutionary conservation) relates to functional importance of the lipid anchor. We present experimental evidence for high-ranked human proteins predicted to be affected by anticancer drugs inhibiting prenylation.
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影响因子：
64.8
作者：
INGLESE, J;KOCH, WJ;LEFKOWITZ, RJ
通讯作者：
LEFKOWITZ, RJ
影响因子：
9.2
作者：
Goto, T;Davidson, L;Keller, R
通讯作者：
Keller, R
法尼化或黄烷基凝聚力？在体外和体内测试蛋白质原始化的有效测定。
影响因子：
--
作者：
Benetka, Wolfgang;Koranda, Manfred;Maurer-Stroh, Sebastian;Pittner, Fritz;Eisenhaber, Frank
通讯作者：
Eisenhaber, Frank
影响因子：
3.4
作者：
Eisenhaber, B;Eisenhaber, F;Neuberger, G
通讯作者：
Neuberger, G
DOI：
10.1073/pnas.89.20.9554
发表时间：
1992-10-15
影响因子：
11.1
作者：
HEILMEYER, LMG;SERWE, M;MEYER, HE
通讯作者：
MEYER, HE