Sequence and structural analysis of BTB domain proteins.
Sequence and structural analysis of BTB domain proteins.
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DOI：
10.1186/gb-2005-6-10-r82
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发表时间：
2005
期刊：
影响因子：
12.3
通讯作者：
Prive, Gilbert G
中科院分区：
文献类型：
--
作者：
Stogios, Peter J;Downs, Gregory S;Jauhal, Jimmy J S;Nandra, Sukhjeen K;Prive, Gilbert G
对17种真核生物BTB结构域蛋白的结构、基因组分布和序列保守性的分析表明，BTB结构域蛋白具有高度的结构保守性，并能适应不同的自结合和与非BTB蛋白相互作用的方式。BTB结构域(也称为POZ结构域)是一个多功能的蛋白质-蛋白质相互作用基序，参与了广泛的细胞功能，包括转录调节、细胞骨架动力学、离子通道组装和门控以及泛素化的靶向蛋白。几个BTB的结构域结构已经被实验确定，揭示了一个高度保守的核心结构。我们研究了17种真核生物BTB结构域蛋白的蛋白质结构、基因组分布和序列保守性。BTB结构域通常在只包含一种或两种其他类型结构域的蛋白质中以单拷贝形式存在，这定义了BTB-锌指(BTB-ZF)、BTB-Back-kelch(BBK)、电压门控钾通道T1(T1-Kv)、Math-BTB、BTB-NPH3和BTB-Back-PHR(BBP)家族等蛋白质。相比之下，Skp1和ElonginC蛋白几乎完全由核心BTB折叠组成。BTB蛋白有大量的谱系特异性扩展，如脊椎动物中相对大量的BTB-ZF和BBK蛋白，秀丽线虫中的Math-BTB蛋白，以及拟南芥中的BTB-NPH3蛋白。利用Skp1和PLZF BTB同源二聚体之间的结构同源性，我们提出了BTB-CUL3 SCF样E3泛素连接酶复合体的模型，表明BTB二聚体或T1四聚体在该复合体中是相容的。尽管序列差异很大，但BTB折叠在结构上是保守的。该折叠已经适应了几种不同的自我结合和与非BTB蛋白相互作用的模式。
An analysis of the protein architecture, genomic distribution and sequence conservation of BTB domain proteins in 17 fully sequenced eukaryotes reveals a high structural conservation and adaptation to different modes of self-association and interactions with non-BTB proteins. The BTB domain (also known as the POZ domain) is a versatile protein-protein interaction motif that participates in a wide range of cellular functions, including transcriptional regulation, cytoskeleton dynamics, ion channel assembly and gating, and targeting proteins for ubiquitination. Several BTB domain structures have been experimentally determined, revealing a highly conserved core structure. We surveyed the protein architecture, genomic distribution and sequence conservation of BTB domain proteins in 17 fully sequenced eukaryotes. The BTB domain is typically found as a single copy in proteins that contain only one or two other types of domain, and this defines the BTB-zinc finger (BTB-ZF), BTB-BACK-kelch (BBK), voltage-gated potassium channel T1 (T1-Kv), MATH-BTB, BTB-NPH3 and BTB-BACK-PHR (BBP) families of proteins, among others. In contrast, the Skp1 and ElonginC proteins consist almost exclusively of the core BTB fold. There are numerous lineage-specific expansions of BTB proteins, as seen by the relatively large number of BTB-ZF and BBK proteins in vertebrates, MATH-BTB proteins in Caenorhabditis elegans, and BTB-NPH3 proteins in Arabidopsis thaliana. Using the structural homology between Skp1 and the PLZF BTB homodimer, we present a model of a BTB-Cul3 SCF-like E3 ubiquitin ligase complex that shows that the BTB dimer or the T1 tetramer is compatible in this complex. Despite widely divergent sequences, the BTB fold is structurally well conserved. The fold has adapted to several different modes of self-association and interactions with non-BTB proteins.