Helicobacter pylori acidic stress response factor HP1286 is a YceI homolog with new binding specificity
Helicobacter pylori acidic stress response factor HP1286 is a YceI homolog with new binding specificity
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DOI：
10.1111/j.1742-4658.2010.07612.x
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发表时间：
2010-04-01
期刊：
影响因子：
5.4
通讯作者：
Zanotti, Giuseppe
中科院分区：
文献类型：
--
作者：
Sisinni, Lorenza;Cendron, Laura;Zanotti, Giuseppe
来自幽门螺杆菌的HP 1286是在胃中细菌定植和持久性中发挥相关作用的蛋白质之一。事实上，它被证明是在酸性胁迫条件下过表达，与其他必要的毒力因子。在这里，我们描述了它的晶体结构，确定在2.1埃的分辨率。的分子模型，一个二聚体的特点是双重对称性，表明HP 1286结构属于YceI样蛋白家族，这反过来又是由脂质运载蛋白折叠的特点。后者的特征是具有结合和/或转运两亲分子功能的内腔的蛋白质。令人惊讶的是，一个分子的芥酸酰胺被发现结合在每个单体的重组HP 1286，克隆和表达在大肠杆菌异源系统的内腔。空腔的形状和长度表明，与该家族的其他成员不同，HP-YceI对具有约22个碳原子的直链的两亲化合物具有结合特异性。这些特征，沿着该蛋白由细菌分泌并参与适应酸性环境的事实，表明其功能可能是从环境中螯合特定的脂肪酸或酰胺，或者为细菌提供其代谢所需的脂肪酸，或保护其免受最终存在于外部环境中的脂肪酸的洗涤剂样抗微生物活性的影响并使其解毒。
HP1286 from Helicobacter pylori is among the proteins that play a relevant role in bacterial colonization and persistence in the stomach. Indeed, it was demonstrated to be overexpressed under acidic stress conditions, together with other essential virulence factors. Here we describe its crystal structure, determined at 2.1 angstrom resolution. The molecular model, a dimer characterized by two-fold symmetry, shows that HP1286 structurally belongs to the YceI-like protein family, which in turn is characterized by the lipocalin fold. The latter characterizes proteins possessing an internal cavity with the function of binding and/or transport of amphiphilic molecules. Surprisingly, a molecule of erucamide was found bound in the internal cavity of each monomer of recombinant HP1286, cloned and expressed in an Escherichia coli heterologous system. The shape and length of the cavity indicate that, at variance with other members of the family, HP-YceI has a binding specificity for amphiphilic compounds with a linear chain of about 22 carbon atoms. These features, along with the fact that the protein is secreted by the bacterium and is involved in adaptation to an acidic environment, suggest that its function could be that of sequestering specific fatty acids or amides from the environment, either to supply the bacterium with the fatty acids necessary for its metabolism, or to protect and detoxify it from the detergent-like antimicrobial activity of fatty acids that are eventually present in the external milieu.