Contributed equally to the work.
The cytoplasmic PASC domain of the sensor kinase DcuS of Escherichia coli: role in signal transduction, dimer formation, and DctA interaction
Article first published online: 9 SEP 2013
© 2013 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Volume 2, Issue 6, pages 912–927, December 2013
How to Cite
MicrobiologyOpen 2013; 2(6): 912–927
- Issue published online: 6 DEC 2013
- Article first published online: 9 SEP 2013
- Manuscript Accepted: 31 JUL 2013
- Manuscript Received: 23 JUL 2013
- Deutsche Forschungsgemeinschaft. Grant Number: (UN 49/8-4, Gr1211/13-3)
- DcuS sensor kinase;
- PAS domain;
- signal transduction.
The cytoplasmic PASC domain of the fumarate responsive sensor kinase DcuS of Escherichia coli links the transmembrane to the kinase domain. PASC is also required for interaction with the transporter DctA serving as a cosensor of DcuS. Earlier studies suggested that PASC functions as a hinge and transmits the signal to the kinase. Reorganizing the PASC dimer interaction and, independently, removal of DctA, converts DcuS to the constitutive ON state (active without fumarate stimulation). ON mutants were categorized with respect to these two biophysical interactions and the functional state of DcuS: type I-ON mutations grossly reorganize the homodimer, and decrease interaction with DctA. Type IIA-ON mutations create the ON state without grossly reorganizing the homodimer, whereas interaction with DctA is decreased. The type IIB-ON mutations were neither in PASC/PASC, nor in DctA/DcuS interaction affected, similar to fumarate activated wild-typic DcuS. OFF mutations never affected dimer stability. The ON mutations provide novel mechanistic insight: PASC dimerization is essential to silence the kinase. Reorganizing the homodimer and its interaction with DctA activate the kinase. The study suggests a novel ON homo-dimer conformation (type IIB) and an OFF conformation for PASC. Type IIB-ON corresponds to the fumarate induced wild-type conformation, representing an interesting target for structural biology.