De Silva Rukman S, Kovacikova Gabriela, Lin Wei, Taylor Ronald K, Skorupski Karen, Kull F Jon
Department of Chemistry, Dartmouth College, Hanover, NH 03755, USA.
J Bacteriol. 2007 Aug;189(15):5683-91. doi: 10.1128/JB.01807-06. Epub 2007 May 25.
Quorum sensing in Vibrio cholerae involves signaling between two-component sensor protein kinases and the response regulator LuxO to control the expression of the master regulator HapR. HapR, in turn, plays a central role in regulating a number of important processes, such as virulence gene expression and biofilm formation. We have determined the crystal structure of HapR to 2.2-A resolution. Its structure reveals a dimeric, two-domain molecule with an all-helical structure that is strongly conserved with members of the TetR family of transcriptional regulators. The N-terminal DNA-binding domain contains a helix-turn-helix DNA-binding motif and alteration of certain residues in this domain completely abolishes the ability of HapR to bind to DNA, alleviating repression of both virulence gene expression and biofilm formation. The C-terminal dimerization domain contains a unique solvent accessible tunnel connected to an amphipathic cavity, which by analogy with other TetR regulators, may serve as a binding pocket for an as-yet-unidentified ligand.
霍乱弧菌中的群体感应涉及双组分传感器蛋白激酶与应答调节因子LuxO之间的信号传导，以控制主要调节因子HapR的表达。反过来，HapR在调节许多重要过程中起着核心作用，例如毒力基因表达和生物膜形成。我们已经确定了HapR的晶体结构，分辨率为2.2埃。其结构揭示了一个二聚体、双结构域分子，具有全螺旋结构，与转录调节因子TetR家族的成员高度保守。N端DNA结合结构域包含一个螺旋-转角-螺旋DNA结合基序，该结构域中某些残基的改变完全消除了HapR与DNA结合的能力，减轻了对毒力基因表达和生物膜形成的抑制。C端二聚化结构域包含一个与两亲性腔相连的独特溶剂可及通道，类似于其他TetR调节因子，它可能作为一个尚未确定的配体的结合口袋。
