Structure of the response regulator PhoP from Mycobacterium tuberculosis reveals a dimer through the receiver domain.
Structure of the response regulator PhoP from Mycobacterium tuberculosis reveals a dimer through the receiver domain.
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DOI：
10.1021/bi2005575
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发表时间：
2011-07-05
期刊：
影响因子：
2.9
通讯作者：
Wang, Shuishu
中科院分区：
文献类型：
--
作者：
Menon, Smita;Wang, Shuishu
来自结核分枝杆菌的PhoP蛋白是OmpR/PhoB亚家族的反应调节因子，其结构由n端受体结构域和c端dna结合结构域组成。由于缺乏全长蛋白的结构信息，目前尚不清楚受体结构域磷酸化如何调节dna结合活性。本文报道结核分枝杆菌全长PhoP的晶体结构。与其他已知的同一亚家族全长蛋白结构不同，PhoP通过其受体结构域形成二聚体，其二聚体界面涉及α4-β5-α5，这是激活的受体结构域二聚体的常见界面。然而，开关残基Thr99和Tyr118的构象与未激活的受体结构域类似。Tyr118侧链参与二聚体界面相互作用。受体结构域通过柔性连接体连接到dna结合结构域，并且不会对dna结合结构域施加结构约束。这种结构表明，磷酸化可能促进/稳定了受体结构域二聚化，使DNA结合结构域更接近，从而增加了它们对直接重复DNA序列的结合亲和力。
The PhoP protein from Mycobacterium tuberculosis is a response regulator of the OmpR/PhoB subfamily, whose structure consists of an N-terminal receiver domain and a C-terminal DNA-binding domain. How the DNA-binding activities are regulated by phosphorylation of the receiver domain remains unclear due to a lack of structural information on the full-length proteins. Here we report the crystal structure of the full-length PhoP of M. tuberculosis. Unlike other known structures of full-length proteins of the same subfamily, PhoP forms a dimer through its receiver domain with the dimer interface involving α4-β5-α5, a common interface for activated receiver domain dimers. However, the switch residues, Thr99 and Tyr118, are in a conformation resembling those of non-activated receiver domains. The Tyr118 side chain is involved in the dimer interface interactions. The receiver domain is tethered to the DNA-binding domain through a flexible linker and does not impose structural constraints on the DNA-binding domain. This structure suggests that phosphorylation likely facilitates/stabilizes receiver domain dimerization, bringing the DNA-binding domains to close proximity, thereby increasing their binding affinity for direct repeat DNA sequences.
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