Structure of the sensor domain of Mycobacterium tuberculosis PknH receptor kinase reveals a conserved binding cleft.

Structure of the sensor domain of Mycobacterium tuberculosis PknH receptor kinase reveals a conserved binding cleft.
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DOI:
10.1016/j.jmb.2012.06.011
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发表时间:
2012-09-28
影响因子:
5.6
通讯作者:
Alber, Tom
Alber, Tom
中科院分区:
生物学2区
文献类型:
--
作者:
Cavazos, Alexandra;Prigozhin, Daniil M.;Alber, Tom

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自二十多年前发现以来,真核样跨膜受体丝氨酸/苏氨酸蛋白激酶(STPKs)被证明在许多细菌的毒力、生长、持久性和再激活中发挥关键作用。然而,关于这些蛋白质传递的信号的信息仍然很少。为了加强对STPK受体信号转导基础的理解,我们测定了结核分枝杆菌受体STPK胞外传感器结构域PKnH(Rv1266c)的1.7?分辨率的晶体结构。PKnH传感器结构域采用了一个出人意料的折叠,其中包含两个分子内的二硫键以及一个大的疏水和极性裂隙。裂隙内的残基和二硫键周围的残基是保守的。这些结果表明,PKnH通过改变激酶域的位置或四级结构与小分子配体结合,从而发出信号。
Since their discovery over twenty years ago, eukaryotic-like transmembrane receptor Ser/Thr protein kinases (STPKs) have been shown to play critical roles in the virulence, growth, persistence and reactivation of many bacteria. Information regarding the signals transmitted by these proteins, however, remains scarce. To enhance understanding of the basis for STPK receptor signaling, we determined the 1.7-Å-resolution crystal structure of the extracellular sensor domain of the Mycobacterium tuberculosis receptor STPK, PknH (Rv1266c). The PknH sensor domain adopts an unanticipated fold containing two intramolecular disulfide bonds and a large hydrophobic and polar cleft. The residues lining the cleft and those surrounding the disulfide bonds are conserved. These results suggest that PknH binds a small-molecule ligand that signals by changing the location or quaternary structure of the kinase domain.
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