Structures of the ligand-binding domain of Helicobacter pylori chemoreceptor TlpA.
Structures of the ligand-binding domain of Helicobacter pylori chemoreceptor TlpA.
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幽门螺杆菌化学感受器 TlpA 的配体结合域的结构。
DOI：
10.1002/pro.3503
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Guillemin,Karen
中科院分区：
文献类型：
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作者：
Sweeney,EmilyG;Perkins,Arden;Kallio,Karen;JamesRemington,Stephen;Guillemin,Karen
细菌使用化学感受器蛋白来感知和导航它们的化学环境。最常见的一类化学感受器是跨膜蛋白，其通过小分子配体与周质结构域的结合来感知化学信号，周质结构域调节受体刺激细胞鞭毛马达逆转的能力。流行的胃病原体幽门螺杆菌使用这种膜结合的化学感受器，称为转换器样蛋白（Tlp），在胃内定植并持续存在。TlpA与精氨酸、碳酸氢盐和酸的传感有关，但没有实验确定的TlpA蛋白质结构可用于更好地理解配体结合和信号转导。在这里，我们报告了TlpA周质部分的三种晶体结构，其中包含串联PAS/Cache结构域，类似于最近发表的乳酸敏感化学受体TlpC的结构。幽门。这些结构是第一个在其天然同源二聚体寡聚体中显示串联PAS/Cache-形式化学受体的结构，并且我们确定了对二聚体界面起关键作用的残基。我们进行了序列分析，以确定TlpA和TlpC同源物，并使用这些同源物之间的残基保守性牵连的一般串联PAS/缓存折叠的重要区域，和特定的TlpA功能的残基。与TlpC的比较表明，尽管在一般结构上具有高度相似性，但TlpA缺乏结合乳酸所需的残基，而是含有本质上几乎完全疏水的口袋。
Bacteria use chemoreceptor proteins to sense and navigate their chemical environments. The most common class of chemoreceptors are transmembrane proteins that sense chemical cues through binding of a small‐molecule ligand to a periplasmic domain, which modulates the receptor's ability to stimulate reversal of the cell's flagella motors. The prevalent gastric pathogenHelicobacter pyloriuses such membrane‐bound chemoreceptors, called transducer‐like proteins (Tlp), to colonize and persist within the stomach. TlpA has been implicated in sensing arginine, bicarbonate, and acid, but no experimentally determined protein structures of TlpA were available to better understand ligand binding and signal transduction. Here, we report three crystal structures of the periplasmic portion of TlpA, which contains tandem PAS/Cache domains, similar to a recently published structure of the lactate‐sensing chemoreceptor TlpC fromH. pylori. These structures are the first to show a tandem PAS/Cache‐form chemoreceptor in its native homo dimer oligomer, and we identify residues that are key contributers to the dimer interface. We performed sequence analyses to identify TlpA and TlpC homologs and used residue conservation among these homologs to implicate regions important for the general tandem PAS/Cache fold, and residues specific to TlpA function. Comparisons with TlpC show that despite high similarity across the general structure, TlpA lacks the residues required to bind lactate, and instead contains a pocket almost entirely hydrophobic in nature.