You are currently viewing the abstract.
View Full TextLog in to view the full text
AAAS login provides access to Science for AAAS members, and access to other journals in the Science family to users who have purchased individual subscriptions.
More options
Download and print this article for your personal scholarly, research, and educational use.
Buy a single issue of Science for just $15 USD.
More than just DNA binding
Specificity between binding partners in bacterial two-component systems, which comprise a histidine kinase sensor and a downstream response regulator, is critical for stimulating appropriate cellular responses to environmental stimuli. Xie et al. solved the crystal structure of the catalytic module of the histidine kinase KdpD in complex with its cognate response regulator KdpE. This structure, in combination with biochemical assays and functional experiments, demonstrated that the DNA binding domain of KdpE contributed to the specific interaction between these partners by interacting with the catalytic domain of KdpD. The KdpD catalytic domain competed with DNA for binding to KdpE, and this interaction was important for the ability of KdpD to stimulate KdpE activity. These findings illustrate a mechanism through which binding specificity may evolve to ensure cognate interactions in two-component systems.
Abstract
Two-component systems (TCSs), which consist of a histidine kinase (HK) sensor and a response regulator (RR), are important for bacteria to quickly sense and respond to various environmental signals. HKs and RRs typically function as a cognate pair, interacting only with one another to transduce signaling. Precise signal transduction in a TCS depends on the specific interactions between the receiver domain (RD) of the RR and the dimerization and histidine phosphorylation domain (DHp) of the HK. Here, we determined the complex structure of KdpDE, a TCS consisting of the HK KdpD and the RR KdpE, which is responsible for K+ homeostasis. Both the RD and the DNA binding domain (DBD) of KdpE interacted with KdpD. Although the RD of KdpE and the DHp of KdpD contributed to binding specificity, the DBD mediated a distinct interaction with the catalytic ATP-binding (CA) domain of KdpD that was indispensable for KdpDE-mediated signal transduction. Moreover, the DBD-CA interface largely overlapped with that of the DBD-DNA complex, leading to competition between KdpD and its target promoter in a KdpE phosphorylation–dependent manner. In addition, the extended C-terminal tail of the CA domain was critical for stabilizing the interaction with KdpDE and for signal transduction. Together, these data provide a molecular basis for specific KdpD and KdpE interactions that play key roles in efficient signal transduction and transcriptional regulation by this TCS.
This is an article distributed under the terms of the Science Journals Default License.
