Sequence motifs and antimotifs in β-barrel membrane proteins from a genome-wide analysis:: The Ala-Tyr dichotomy and chaperone binding motifs
Sequence motifs and antimotifs in β-barrel membrane proteins from a genome-wide analysis:: The Ala-Tyr dichotomy and chaperone binding motifs
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DOI：
10.1016/j.jmb.2006.07.095
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发表时间：
2006-10-20
影响因子：
5.6
通讯作者：
Liang, Jie
中科院分区：
文献类型：
--
作者：
Jackups, Ronald, Jr.;Cheng, Sarah;Liang, Jie
在革兰氏阴性细菌、线粒体和叶绿体的外膜中发现β-桶膜蛋白。尽管序列基序在α-螺旋膜蛋白中已被研究，并已被证明在其组装中起重要作用，但尚不清楚β-桶膜蛋白中是否存在过度表达的基序和代表不足的反基序。我们已经开发了概率模型来识别由任意数量的残基分开的同一条链上的残基对的序列基序。一个严格的统计模型是必不可少的，因为这项研究的困难与短链的长度和少量的结构数据。通过与同一β链内残基完全置换的空模型的比较，利用我们开发的几个分析公式或枚举法精确计算了两个残基序列模式的倾向值和衡量统计显著性的p值。我们发现跨膜（TM）链中存在特征性的序列基序和反基序。氨基酸Tyr在几个这样的基序中起重要作用。我们发现了一个一般的二分法，包括有利的脂肪族-酪氨酸序列基序和不利的酪氨酸-脂肪族反基序。Tyr也是末端基序YxF的一部分，YxF可能对伴侣结合很重要。我们的研究结果还建议几个实验，可以帮助阐明在体外和体内折叠的β-桶膜蛋白的机制。(c)2006爱思唯尔有限公司保留所有权利。
beta-barrel membrane proteins are found in the outer membrane of gramnegative bacteria, mitochondria, and chloroplasts. Although sequence motifs have been studied in a-helical membrane proteins and have been shown to play important roles in their assembly, it is not clear whether overrepresented motifs and under-represented anti-motifs exist in beta-barrel membrane proteins. We have developed probabilistic models to identify sequence motifs of residue pairs on the same strand separated by an arbitrary number of residues. A rigorous statistical model is essential for this study because of the difficulty associated with the short length of the strands and the small amount of structural data. By comparing to the null model of exhaustive permutation of residues within the same beta-strand, propensity values of sequence patterns of two residues and p-values measuring statistical significance are calculated exactly by several analytical formulae we have developed or by enumeration. We find that there are characteristic sequence motifs and antimotifs in transmembrane (TM) strands. The amino acid Tyr plays an important role in several such motifs. We find a general dichotomy consisting of favorable Aliphatic-Tyr sequence motifs and unfavorable Tyr-Aliphatic antimotifs. Tyr is also part of a terminal motif, YxF, which is likely to be important for chaperone binding. Our results also suggest several experiments that can help to elucidate the mechanisms of in vitro and in vivo folding of beta-barrel membrane proteins. (c) 2006 Elsevier Ltd. All rights reserved.