A short intrinsically disordered region at KtrB’s N-terminus facilitates allosteric regulation of K+ channel KtrAB
Abstract K+ homeostasis is crucial for bacterial survival. The bacterial K+ channel KtrAB is regulated by the binding of ADP and ATP to the cytosolic RCK subunits KtrA. While the ligand-induced conformational changes in KtrA are well described, the transmission to the gating regions within KtrB is n...
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| Format: | Article |
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Nature Portfolio
2025-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-59546-z |
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| _version_ | 1850190525053796352 |
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| author | Janina Stautz David Griwatz Susann Kaltwasser Ahmad Reza Mehdipour Sophie Ketter Celina Thiel Dorith Wunnicke Marina Schrecker Deryck J. Mills Gerhard Hummer Janet Vonck Inga Hänelt |
| author_facet | Janina Stautz David Griwatz Susann Kaltwasser Ahmad Reza Mehdipour Sophie Ketter Celina Thiel Dorith Wunnicke Marina Schrecker Deryck J. Mills Gerhard Hummer Janet Vonck Inga Hänelt |
| author_sort | Janina Stautz |
| collection | DOAJ |
| description | Abstract K+ homeostasis is crucial for bacterial survival. The bacterial K+ channel KtrAB is regulated by the binding of ADP and ATP to the cytosolic RCK subunits KtrA. While the ligand-induced conformational changes in KtrA are well described, the transmission to the gating regions within KtrB is not understood. Here, we present a cryo-EM structure of the ADP-bound, inactive KtrAB complex from Vibrio alginolyticus, which resolves part of KtrB’s N termini. They are short intrinsically disordered regions (IDRs) located at the interface of KtrA and KtrB. We reveal that these IDRs play a decisive role in ATP-mediated channel opening, while the closed ADP-bound state does not depend on the N-termini. We propose an allosteric mechanism, in which ATP-induced conformational changes within KtrA trigger an interaction of KtrB’s N-terminal IDRs with the membrane, stabilizing the active and conductive state of KtrAB. |
| format | Article |
| id | doaj-art-d2d67be71da04a1285cbd163346a9857 |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-d2d67be71da04a1285cbd163346a98572025-08-20T02:15:15ZengNature PortfolioNature Communications2041-17232025-05-0116111610.1038/s41467-025-59546-zA short intrinsically disordered region at KtrB’s N-terminus facilitates allosteric regulation of K+ channel KtrABJanina Stautz0David Griwatz1Susann Kaltwasser2Ahmad Reza Mehdipour3Sophie Ketter4Celina Thiel5Dorith Wunnicke6Marina Schrecker7Deryck J. Mills8Gerhard Hummer9Janet Vonck10Inga Hänelt11Institute of Biochemistry, Goethe University FrankfurtInstitute of Biochemistry, Goethe University FrankfurtCentral Electron Microscopy Facility, Max Planck Institute of BiophysicsCenter for Molecular Modeling, Ghent UniversityInstitute of Biochemistry, Goethe University FrankfurtInstitute of Biochemistry, Goethe University FrankfurtInstitute of Biochemistry, Goethe University FrankfurtInstitute of Biochemistry, Goethe University FrankfurtDepartment of Structural Biology, Max Planck Institute of BiophysicsDepartment of Theoretical Biophysics, Max Planck Institute of BiophysicsDepartment of Structural Biology, Max Planck Institute of BiophysicsInstitute of Biochemistry, Goethe University FrankfurtAbstract K+ homeostasis is crucial for bacterial survival. The bacterial K+ channel KtrAB is regulated by the binding of ADP and ATP to the cytosolic RCK subunits KtrA. While the ligand-induced conformational changes in KtrA are well described, the transmission to the gating regions within KtrB is not understood. Here, we present a cryo-EM structure of the ADP-bound, inactive KtrAB complex from Vibrio alginolyticus, which resolves part of KtrB’s N termini. They are short intrinsically disordered regions (IDRs) located at the interface of KtrA and KtrB. We reveal that these IDRs play a decisive role in ATP-mediated channel opening, while the closed ADP-bound state does not depend on the N-termini. We propose an allosteric mechanism, in which ATP-induced conformational changes within KtrA trigger an interaction of KtrB’s N-terminal IDRs with the membrane, stabilizing the active and conductive state of KtrAB.https://doi.org/10.1038/s41467-025-59546-z |
| spellingShingle | Janina Stautz David Griwatz Susann Kaltwasser Ahmad Reza Mehdipour Sophie Ketter Celina Thiel Dorith Wunnicke Marina Schrecker Deryck J. Mills Gerhard Hummer Janet Vonck Inga Hänelt A short intrinsically disordered region at KtrB’s N-terminus facilitates allosteric regulation of K+ channel KtrAB Nature Communications |
| title | A short intrinsically disordered region at KtrB’s N-terminus facilitates allosteric regulation of K+ channel KtrAB |
| title_full | A short intrinsically disordered region at KtrB’s N-terminus facilitates allosteric regulation of K+ channel KtrAB |
| title_fullStr | A short intrinsically disordered region at KtrB’s N-terminus facilitates allosteric regulation of K+ channel KtrAB |
| title_full_unstemmed | A short intrinsically disordered region at KtrB’s N-terminus facilitates allosteric regulation of K+ channel KtrAB |
| title_short | A short intrinsically disordered region at KtrB’s N-terminus facilitates allosteric regulation of K+ channel KtrAB |
| title_sort | short intrinsically disordered region at ktrb s n terminus facilitates allosteric regulation of k channel ktrab |
| url | https://doi.org/10.1038/s41467-025-59546-z |
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