Calcium ions modulate amino acid sensing of the chemoreceptor Mlp24 of Vibrio cholerae
Calcium ions modulate amino acid sensing of the chemoreceptor Mlp24 of Vibrio cholerae
复制标题
钙离子调节霍乱弧菌化学感受器 Mlp24 的氨基酸感应
DOI：
10.1128/jb.00779-18
复制
发表时间：
2019
影响因子：
3.2
通讯作者：
K. Imada
中科院分区：
文献类型：
--
作者：
Y. Takahashi;S. Nishiyama;K. Sumita;I. Kawagishi;K. Imada
细菌使用化学传感器蛋白来感知环境化学物质，其中大部分存在于细胞膜中。典型的化学受体在其周质区域结合它们的特定配体，而配体结合产生一个分子刺激，该刺激被传递到细胞质，导致各种细胞反应，如趋化和特异性基因表达。霍乱弧菌是霍乱的病原体，含有约44个可能的感受器蛋白，这些蛋白与参与趋化作用的甲基接受趋化蛋白同源。其中两个，Mlp24和Mlp37，已被鉴定为化学受体，介导对各种氨基酸的趋化反应。虽然参与配体结合的大部分Mlp37残基在Mlp24中是保守的，但这些化学受体以不同的亲和力结合相同的配体。此外，它们还具有不同的细胞角色。在这里，我们确定了Mlp24(Mlp24p)的周质结构域的一系列配体络合物结构。结构显示，Ca~(2+)与形成配体结合袋上壁的环结合。Ca2+不与Mlp37的相应环结合，表明环的结构差异可能导致配体亲和力的差异。等温滴定热法(ITC)测量表明，钙离子改变了Mlp24p的配基结合亲和力。此外，Ca~(2+)影响Mlp24介导的多种氨基酸的趋化行为。因此，建议钙离子作为Mlp24p介导的初级信号的辅助信号，霍乱弧菌通过调节Mlp24的配基敏感性来微调其趋化行为，依赖于钙离子的浓度。虽然大多数参与配体相互作用的残基都是保守的，但这些化学受体对同一配体表现出不同的亲和力，发挥着不同的细胞作用。Mlp24(Mlp24p)周质区域的一系列配基复合体结构和ITC分析表明，钙离子与Mlp24p的环结合并调节Mlp24p的配体结合亲和力。此外，钙离子改变了Mlp24介导的趋化行为。我们认为，Ca~(2+)作为共信号调节Mlp24对初级信号的亲和力，从而改变霍乱弧菌的趋化行为。
Bacteria sense environmental chemicals using chemosensor proteins, most of which are present in the cytoplasmic membrane. Canonical chemoreceptors bind their specific ligands in their periplasmic domain, and the ligand binding creates a molecular stimulus that is transmitted into the cytoplasm, leading to various cellular responses, such as chemotaxis and specific gene expression. Vibrio cholerae, the causative agent of cholera, contains about 44 putative sensor proteins, which are homologous to methyl-accepting chemotaxis proteins involved in chemotaxis. Two of them, Mlp24 and Mlp37, have been identified as chemoreceptors that mediate chemotactic responses to various amino acids. Although most of the residues of Mlp37 involved in ligand binding are conserved in Mlp24, these chemoreceptors bind the same ligands with different affinities. Moreover, they have distinct cellular roles. Here we determined a series of ligand complex structures of the periplasmic domains of Mlp24 (Mlp24p). The structures revealed that Ca2+binds to the loop that forms the upper wall of the ligand-binding pocket. Ca2+does not bind to the corresponding loop of Mlp37, implying that the structural difference of the loop may cause the ligand affinity difference. Isothermal titration calorimetry (ITC) measurements indicated that Ca2+changes the ligand binding affinity of Mlp24p. Furthermore, Ca2+affected chemotactic behaviors to various amino acids mediated by Mlp24. Thus, Ca2+is suggested to serve as a cosignal for the primary signal mediated by Mlp24p, and V. cholerae fine-tunes its chemotactic behavior depending on the Ca2+concentration by modulating the ligand sensitivity of Mlp24.IMPORTANCEMlp24 and Mlp37 are homologous chemoreceptors of Vibrio cholerae that bind various amino acids. Although most of the residues involved in ligand interaction are conserved, these chemoreceptors show different affinities for the same ligand and play different cellular roles. A series of ligand complex structures of the periplasmic region of Mlp24 (Mlp24p) and following ITC analysis revealed that Ca2+binds to the loop of Mlp24p and modulates the ligand binding affinity of Mlp24p. Moreover, Ca2+changes the chemotactic behaviors mediated by Mlp24. We propose that Ca2+acts as a cosignal that modulates the affinity of Mlp24 for the primary signal, thereby changing the chemotactic behavior of V. cholerae.