Stogios Peter J, Downs Gregory S, Jauhal Jimmy J S, Nandra Sukhjeen K, Privé Gilbert G
Department of Medical Biophysics, University of Toronto, Toronto, Ontario, M5G 2M9, Canada.
Genome Biol. 2005;6(10):R82. doi: 10.1186/gb-2005-6-10-r82. Epub 2005 Sep 15.
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.
BTB结构域(也称为POZ结构域)是一种多功能的蛋白质-蛋白质相互作用基序,参与多种细胞功能,包括转录调控、细胞骨架动力学、离子通道组装与门控以及将蛋白质靶向泛素化。已经通过实验确定了几种BTB结构域的结构,揭示了一个高度保守的核心结构。
我们调查了17种全基因组测序的真核生物中BTB结构域蛋白的蛋白质结构、基因组分布和序列保守性。BTB结构域通常在仅包含一两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)等蛋白质家族。相比之下,Skp1和ElonginC蛋白几乎完全由核心BTB折叠组成。BTB蛋白有许多谱系特异性的扩增,如脊椎动物中相对大量的BTB-ZF和BBK蛋白、秀丽隐杆线虫中的MATH-BTB蛋白以及拟南芥中的BTB-NPH3蛋白所示。利用Skp1与PLZF BTB同型二聚体之间的结构同源性,我们提出了一种BTB-Cul3 SCF样E3泛素连接酶复合物模型,该模型表明BTB二聚体或T1四聚体在该复合物中是兼容的。
尽管序列差异很大,但BTB折叠在结构上高度保守。该折叠已适应几种不同的自组装模式以及与非BTB蛋白的相互作用。