WXG100 protein superfamily consists of three subfamilies and exhibits an α-helical C-terminal conserved residue pattern.
WXG100 protein superfamily consists of three subfamilies and exhibits an α-helical C-terminal conserved residue pattern.
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DOI：
10.1371/journal.pone.0089313
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Song YH
中科院分区：
文献类型：
--
作者：
Poulsen C;Panjikar S;Holton SJ;Wilmanns M;Song YH
WXG100 蛋白超家族的成员形成同二聚体或异二聚体复合物。其中研究最多的蛋白质是来自结核分枝杆菌的分泌型 T 细胞抗原 CFP-10（10 kDa 培养滤液蛋白，EsxB）和 ESAT-6（6 kDa 早期分泌抗原靶标，EsxA）。它们由基因簇内的操纵子编码，该基因簇名为 ESX-1，编码 VII 型分泌系统 (T7SS)。 WXG100蛋白以全长形式分泌，并且已知它们采用四螺旋束结构。在当前的工作中，我们讨论了同二聚体和异二聚体 WXG100 蛋白之间的进化关系、寡聚状态的基础以及 WXG100 蛋白保守序列模式的关键结构特征。我们对 WXG100 蛋白超家族进行了迭代生物信息学分析，并将其与代表性 WXG100 蛋白的原子结构相关联。首先，我们发现 WXG100 蛋白超家族由三个亚家族组成：CFP-10、ESAT-6 和 sagEsxA 样蛋白（EsxA 蛋白与无乳链球菌相似）。其次，异二聚体复合物可能是从同二聚体前体进化而来的。第三，异二聚体 WXG100 蛋白的基因总是由双顺反子操纵子编码，最后，通过将序列比对与 X 射线数据相结合，我们识别出保守的 C 端序列模式。这些保守残基的侧链装饰 C 端 α 螺旋的同一侧，因此形成独特的表面。我们的结果得出了推定的扩展的 T7SS 分泌信号，该信号结合了两个报道的 T7SS 识别特征：首先，T7SS 分泌信号位于 T7SS 底物的 C 末端，其次，保守残基 YxxxD/E 对于 T7SS 活性至关重要。此外，我们提出由包含 YxxxD/E 基序的保守序列模式形成的特定 α 螺旋表面是 T7SS 底物识别的关键组成部分。
Members of the WXG100 protein superfamily form homo- or heterodimeric complexes. The most studied proteins among them are the secreted T-cell antigens CFP-10 (10 kDa culture filtrate protein, EsxB) and ESAT-6 (6 kDa early secreted antigen target, EsxA) from Mycobacterium tuberculosis. They are encoded on an operon within a gene cluster, named as ESX-1, that encodes for the Type VII secretion system (T7SS). WXG100 proteins are secreted in a full-length form and it is known that they adopt a four-helix bundle structure. In the current work we discuss the evolutionary relationship between the homo- and heterodimeric WXG100 proteins, the basis of the oligomeric state and the key structural features of the conserved sequence pattern of WXG100 proteins. We performed an iterative bioinformatics analysis of the WXG100 protein superfamily and correlated this with the atomic structures of the representative WXG100 proteins. We find, firstly, that the WXG100 protein superfamily consists of three subfamilies: CFP-10-, ESAT-6- and sagEsxA-like proteins (EsxA proteins similar to that of Streptococcus agalactiae). Secondly, that the heterodimeric complexes probably evolved from a homodimeric precursor. Thirdly, that the genes of hetero-dimeric WXG100 proteins are always encoded in bi-cistronic operons and finally, by combining the sequence alignments with the X-ray data we identify a conserved C-terminal sequence pattern. The side chains of these conserved residues decorate the same side of the C-terminal α-helix and therefore form a distinct surface. Our results lead to a putatively extended T7SS secretion signal which combines two reported T7SS recognition characteristics: Firstly that the T7SS secretion signal is localized at the C-terminus of T7SS substrates and secondly that the conserved residues YxxxD/E are essential for T7SS activity. Furthermore, we propose that the specific α-helical surface formed by the conserved sequence pattern including YxxxD/E motif is a key component of T7SS-substrate recognition.
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影响因子：
4.8
作者：
Lightbody, Kirsty L.;Ilghari, Dariush;Carr, Mark D.
通讯作者：
Carr, Mark D.
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
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作者：
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通讯作者：
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DOI：
10.1073/pnas.1119453109
发表时间：
2012-07-10
影响因子：
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作者：
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