Substitutions in the redox-sensing PAS domain of the NifL regulatory protein define an inter-subunit pathway for redox signal transmission

Little, Richard, Salinas, Paloma, Slavny, Peter, Clarke, Thomas A. and Dixon, Ray (2011) Substitutions in the redox-sensing PAS domain of the NifL regulatory protein define an inter-subunit pathway for redox signal transmission. Molecular Microbiology, 82 (1). pp. 222-235. ISSN 1365-2958

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Abstract

The Per-ARNT-Sim (PAS) domain is a conserved a/ß fold present within a plethora of signalling proteins from all kingdoms of life. PAS domains are often dimeric and act as versatile sensory and interaction modules to propagate environmental signals to effector domains. The NifL regulatory protein from Azotobacter vinelandii senses the oxygen status of the cell via an FAD cofactor accommodated within the first of two amino-terminal tandem PAS domains, termed PAS1 and PAS2. The redox signal perceived at PAS1 is relayed to PAS2 resulting in conformational reorganization of NifL and consequent inhibition of NifA activity. We have identified mutations in the cofactor-binding cavity of PAS1 that prevent 'release' of the inhibitory signal upon oxidation of FAD. Substitutions of conserved ß-sheet residues on the distal surface of the FAD-binding cavity trap PAS1 in the inhibitory signalling state, irrespective of the redox state of the FAD group. In contrast, substitutions within the flanking A'a-helix that comprises part of the dimerization interface of PAS1 prevent transmission of the inhibitory signal. Taken together, these results suggest an inter-subunit pathway for redox signal transmission from PAS1 that propagates from core to the surface in a conformation-dependent manner requiring a flexible dimer interface.

Item Type: Article
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Faculty of Science > School of Biological Sciences
Depositing User: Users 2731 not found.
Date Deposited: 03 Oct 2011 13:16
Last Modified: 17 Sep 2020 23:30
URI: https://ueaeprints.uea.ac.uk/id/eprint/34933
DOI: 10.1111/j.1365-2958.2011.07812.x

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