Structural Studies of Potassium Transport Protein KtrA Regulator of Conductance of K+ (RCK) C Domain in Complex with Cyclic Diadenosine Monophosphate (c-di-AMP)
Structural Studies of Potassium Transport Protein KtrA Regulator of Conductance of K+ (RCK) C Domain in Complex with Cyclic Diadenosine Monophosphate (c-di-AMP)
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DOI：
10.1074/jbc.m115.641340
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发表时间：
2015-06-26
影响因子：
4.8
通讯作者：
Choi, Byong-Seok
中科院分区：
文献类型：
--
作者：
Kim, Henna;Youn, Suk-Jun;Choi, Byong-Seok
背景：环二AMP使KtrA的钾转运活性失活。结果：环二AMP与KrtA结合可引起构象变化。结论：环二AMP选择性地与KtrA RCK_C结构域结合，并发出钾转运失活信号。意义：研究了环二AMP在钾通道活性中作用的分子基础。虽然它最近才被确定为第二信使，但c-双AMP被发现在许多细菌功能中具有基础作用，如离子转运。钾转运蛋白KtrA被鉴定为c-di-AMP受体。然而，c-di-AMP与蛋白质的共结晶还没有得到研究。在这里，我们测定了与c-diAMP络合物中KtrA RCK_C结构域的晶体结构。C-di-AMP核苷酸呈U型构象，结合在RCK_C的二聚体界面，靠近螺旋3和4。c-di-AMP主要通过形成氢键和疏水作用与KtrA RCK_C相互作用。C-di-AMP结合诱导二聚体收缩，使KtrA RCK_C的两个单体更接近。KtrA RCK_C只能与c-di-AMP相互作用，不能与c-di-GMP、3，3-cGAMP、ATP和ADP相互作用。KtrA RCK_C结构域和c-di-AMP复合体的结构有助于我们理解c-di-AMP调控的Ktr转运体失活机制。
Background: Cyclic di-AMP inactivates the potassium transport activity of KtrA. Results: Cyclic di-AMP binding to KrtA induced conformational changes. Conclusion: Cyclic di-AMP selectively binds to the KtrA RCK_C domain and signals the inactivation of potassium transport. Significance: The molecular basis for the role of cyclic di-AMP in potassium channel activity was investigated.Although it was only recently identified as a second messenger, c-di-AMP was found to have fundamental importance in numerous bacterial functions such as ion transport. The potassium transporter protein, KtrA, was identified as a c-di-AMP receptor. However, the co-crystallization of c-di-AMP with the protein has not been studied. Here, we determined the crystal structure of the KtrA RCK_C domain in complex with c-di-AMP. The c-di-AMP nucleotide, which adopts a U-shaped conformation, is bound at the dimer interface of RCK_C close to helices 3 and 4. c-di-AMP interacts with KtrA RCK_C mainly by forming hydrogen bonds and hydrophobic interactions. c-di-AMP binding induces the contraction of the dimer, bringing the two monomers of KtrA RCK_C into close proximity. The KtrA RCK_C was able to interact with only c-di-AMP, but not with c-di-GMP, 3,3-cGAMP, ATP, and ADP. The structure of the KtrA RCK_C domain and c-di-AMP complex would expand our understanding about the mechanism of inactivation in Ktr transporters governed by c-di-AMP.