School of Molecular Bioscience, University of Sydney, NSW 2006, Australia.
J Mol Biol. 2011 Jan 7;405(1):214-26. doi: 10.1016/j.jmb.2010.10.047. Epub 2010 Nov 2.
In Bacillus subtilis, the KipI protein is a regulator of the phosphorelay governing the onset of sporulation. KipI binds the relevant sensor histidine kinase, KinA, and inhibits the autophosphorylation reaction. Gene homologues of kipI are found almost ubiquitously throughout the bacterial kingdom and are usually located adjacent to, and often fused with, kipA gene homologues. In B. subtilis, the KipA protein inhibits the antikinase activity of KipI thereby permitting sporulation. We have used a combination of biophysical techniques in order to understand the domain structure and shape of the KipI-KipA complex and probe the nature of the interaction. We also have solved the crystal structure of TTHA0988, a Thermus thermophilus protein of unknown function that is homologous to a KipI-KipA fusion. This structure, which is the first to be described for this class of proteins, provides unique insight into the nature of the KipI-KipA complex. The structure confirms that KipI and KipA are proteins with two domains, and the C-terminal domains belong to the cyclophilin family. These cyclophilin domains are positioned in the complex such that their conserved surfaces face each other to form a large "bicyclophilin" cleft. We discuss the sequence conservation and possible roles across species of this near-ubiquitous protein family, which is poorly understood in terms of function.
在枯草芽孢杆菌中，KipI 蛋白是磷酸接力系统的调控因子，该系统控制孢子形成的开始。KipI 结合相关的传感器组氨酸激酶 KinA，并抑制其自身磷酸化反应。kipI 的基因同源物几乎在整个细菌王国中普遍存在，通常位于邻近位置，并且经常与 kipA 基因同源物融合。在枯草芽孢杆菌中，KipA 蛋白抑制 KipI 的抗激酶活性，从而允许孢子形成。我们使用了一系列生物物理技术来了解 KipI-KipA 复合物的结构和形状，并探究其相互作用的本质。我们还解决了 TTHA0988 的晶体结构，TTHA0988 是一种来自 Thermus thermophilus 的未知功能的蛋白，与 KipI-KipA 融合蛋白同源。该结构是该类蛋白的首个描述，为 KipI-KipA 复合物的本质提供了独特的见解。该结构证实 KipI 和 KipA 是具有两个结构域的蛋白，C 端结构域属于亲环素家族。这些亲环素结构域在复合物中的位置使得它们的保守表面彼此相对，形成一个大的“双亲环素”裂缝。我们讨论了这个普遍存在的蛋白家族在物种间的序列保守性和可能作用，尽管该家族在功能方面了解甚少。
