AMP binding stabilizes the KTN domain of the Shewanella denitrificans Kef potassium efflux system
Ligand binding is one of the most fundamental properties of proteins. Ligand functions fall into three basic types: substrates, regulatory molecules, and co-factors essential to protein stability, reactivity, or enzyme-substrate complex formation. The regulation of potassium ion movement in bacteria...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
American Chemical Society
2017
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| _version_ | 1797054362066878464 |
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| author | Pliotas, C Grayer, S Ekkerman, S Chan, A Healy, J Marius, P Bartlett, W Khan, A Cortopassi, W Chandler, S Rasmussen, T Benesch, J Paton, R Claridge, T Miller, S Booth, I Naismith, J Conway, S |
| author_facet | Pliotas, C Grayer, S Ekkerman, S Chan, A Healy, J Marius, P Bartlett, W Khan, A Cortopassi, W Chandler, S Rasmussen, T Benesch, J Paton, R Claridge, T Miller, S Booth, I Naismith, J Conway, S |
| author_sort | Pliotas, C |
| collection | OXFORD |
| description | Ligand binding is one of the most fundamental properties of proteins. Ligand functions fall into three basic types: substrates, regulatory molecules, and co-factors essential to protein stability, reactivity, or enzyme-substrate complex formation. The regulation of potassium ion movement in bacteria is predominantly under the control of regulatory ligands that gate the relevant channels and transporters, which possess subunits or domains that contain Rossmann folds (RFs). Here we demonstrate that AMP is bound to both RFs of the dimeric bacterial Kef potassium efflux system (Kef), where it plays a structural role. We conclude that AMP binds with high affinity ensuring that the site is fully occupied at all times in the cell. Loss of the ability to bind AMP, we demonstrate, causes protein, and likely dimer, instability and consequent loss of function. Regulation of Kef system function is via the reversible binding of comparatively low affinity glutathione-based ligands at the interface between the dimer subunits. We propose this interfacial binding site is itself stabilised, at least in part, by AMP binding. |
| first_indexed | 2024-03-06T18:56:12Z |
| format | Journal article |
| id | oxford-uuid:11ee88d0-6699-4a63-9418-89f9ac7057c3 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:56:12Z |
| publishDate | 2017 |
| publisher | American Chemical Society |
| record_format | dspace |
| spelling | oxford-uuid:11ee88d0-6699-4a63-9418-89f9ac7057c32022-03-26T10:04:59ZAMP binding stabilizes the KTN domain of the Shewanella denitrificans Kef potassium efflux systemJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:11ee88d0-6699-4a63-9418-89f9ac7057c3EnglishSymplectic Elements at OxfordAmerican Chemical Society2017Pliotas, CGrayer, SEkkerman, SChan, AHealy, JMarius, PBartlett, WKhan, ACortopassi, WChandler, SRasmussen, TBenesch, JPaton, RClaridge, TMiller, SBooth, INaismith, JConway, SLigand binding is one of the most fundamental properties of proteins. Ligand functions fall into three basic types: substrates, regulatory molecules, and co-factors essential to protein stability, reactivity, or enzyme-substrate complex formation. The regulation of potassium ion movement in bacteria is predominantly under the control of regulatory ligands that gate the relevant channels and transporters, which possess subunits or domains that contain Rossmann folds (RFs). Here we demonstrate that AMP is bound to both RFs of the dimeric bacterial Kef potassium efflux system (Kef), where it plays a structural role. We conclude that AMP binds with high affinity ensuring that the site is fully occupied at all times in the cell. Loss of the ability to bind AMP, we demonstrate, causes protein, and likely dimer, instability and consequent loss of function. Regulation of Kef system function is via the reversible binding of comparatively low affinity glutathione-based ligands at the interface between the dimer subunits. We propose this interfacial binding site is itself stabilised, at least in part, by AMP binding. |
| spellingShingle | Pliotas, C Grayer, S Ekkerman, S Chan, A Healy, J Marius, P Bartlett, W Khan, A Cortopassi, W Chandler, S Rasmussen, T Benesch, J Paton, R Claridge, T Miller, S Booth, I Naismith, J Conway, S AMP binding stabilizes the KTN domain of the Shewanella denitrificans Kef potassium efflux system |
| title | AMP binding stabilizes the KTN domain of the Shewanella denitrificans Kef potassium efflux system |
| title_full | AMP binding stabilizes the KTN domain of the Shewanella denitrificans Kef potassium efflux system |
| title_fullStr | AMP binding stabilizes the KTN domain of the Shewanella denitrificans Kef potassium efflux system |
| title_full_unstemmed | AMP binding stabilizes the KTN domain of the Shewanella denitrificans Kef potassium efflux system |
| title_short | AMP binding stabilizes the KTN domain of the Shewanella denitrificans Kef potassium efflux system |
| title_sort | amp binding stabilizes the ktn domain of the shewanella denitrificans kef potassium efflux system |
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