综合生物信息学和计算生物学方法鉴定新的BH3-Only候选蛋白。

Robert G Hawley, Yuzhong Chen, Irene Riz, Chen Zeng
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引用次数: 14

摘要

在这项研究中,我们利用综合生物信息学和计算生物学的方法来寻找新的BH3-only蛋白属于BCL2家族的凋亡调节因子。BH3 (BCL2同源3)结构域介导不同BCL2家族成员之间的特异性结合相互作用。它由大约13个残基的两亲α-螺旋区组成,只有少数氨基酸在所有成员中高度保守。利用广义基序,我们在NCBI共识编码序列(CCDS)数据库中进行了全基因组搜索,寻找新的含有bh3的蛋白质。除了已知的促凋亡的BH3-only蛋白外,还恢复了197个满足搜索标准的蛋白。采用位置特异性评分矩阵模型,根据α-螺旋含量和BCL-xL(由BCL2L1编码)和MCL-1这两个抗凋亡BCL2家族成员的预测结合进行分类。值得注意的是,该列表丰富了与自噬相关的蛋白质,以及广泛的细胞应激反应,如内质网应激、氧化应激、抗病毒防御和DNA损伤反应。强调了几种潜在的新型含bh3蛋白。特别是,分析强烈表明,细胞凋亡抑制剂和DNA损伤反应调节因子AVEN,最初是作为bcl - xl相互作用蛋白分离出来的,是一个功能性的bh3蛋白,代表了BCL2家族成员的一个不同亚类。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

An Integrated Bioinformatics and Computational Biology Approach Identifies New BH3-Only Protein Candidates.

An Integrated Bioinformatics and Computational Biology Approach Identifies New BH3-Only Protein Candidates.

In this study, we utilized an integrated bioinformatics and computational biology approach in search of new BH3-only proteins belonging to the BCL2 family of apoptotic regulators. The BH3 (BCL2 homology 3) domain mediates specific binding interactions among various BCL2 family members. It is composed of an amphipathic α-helical region of approximately 13 residues that has only a few amino acids that are highly conserved across all members. Using a generalized motif, we performed a genome-wide search for novel BH3-containing proteins in the NCBI Consensus Coding Sequence (CCDS) database. In addition to known pro-apoptotic BH3-only proteins, 197 proteins were recovered that satisfied the search criteria. These were categorized according to α-helical content and predictive binding to BCL-xL (encoded by BCL2L1) and MCL-1, two representative anti-apoptotic BCL2 family members, using position-specific scoring matrix models. Notably, the list is enriched for proteins associated with autophagy as well as a broad spectrum of cellular stress responses such as endoplasmic reticulum stress, oxidative stress, antiviral defense, and the DNA damage response. Several potential novel BH3-containing proteins are highlighted. In particular, the analysis strongly suggests that the apoptosis inhibitor and DNA damage response regulator, AVEN, which was originally isolated as a BCL-xL-interacting protein, is a functional BH3-only protein representing a distinct subclass of BCL2 family members.

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