دورية أكاديمية
Allosteric mechanism of signal transduction in the two-component system histidine kinase PhoQ
| العنوان: | Allosteric mechanism of signal transduction in the two-component system histidine kinase PhoQ |
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| المؤلفون: | Bruk Mensa, Nicholas F Polizzi, Kathleen S Molnar, Andrew M Natale, Thomas Lemmin, William F DeGrado |
| المصدر: | eLife, Vol 10 (2021) |
| بيانات النشر: | eLife Sciences Publications Ltd, 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Medicine LCC:Science LCC:Biology (General) |
| مصطلحات موضوعية: | histidine kinase, signal transduction, HAMP, PhoQ, allostery, Medicine, Science, Biology (General), QH301-705.5 |
| الوصف: | Transmembrane signaling proteins couple extracytosolic sensors to cytosolic effectors. Here, we examine how binding of Mg2+ to the sensor domain of an E. coli two component histidine kinase (HK), PhoQ, modulates its cytoplasmic kinase domain. We use cysteine-crosslinking and reporter-gene assays to simultaneously and independently probe the signaling state of PhoQ’s sensor and autokinase domains in a set of over 30 mutants. Strikingly, conservative single-site mutations distant from the sensor or catalytic site strongly influence PhoQ’s ligand-sensitivity as well as the magnitude and direction of the signal. Data from 35 mutants are explained by a semi-empirical three-domain model in which the sensor, intervening HAMP, and catalytic domains can adopt kinase-promoting or inhibiting conformations that are in allosteric communication. The catalytic and sensor domains intrinsically favor a constitutively ‘kinase-on’ conformation, while the HAMP domain favors the ‘off’ state; when coupled, they create a bistable system responsive to physiological concentrations of Mg2+. Mutations alter signaling by locally modulating domain intrinsic equilibrium constants and interdomain couplings. Our model suggests signals transmit via interdomain allostery rather than propagation of a single concerted conformational change, explaining the diversity of signaling structural transitions observed in individual HK domains. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2050-084X |
| Relation: | https://elifesciences.org/articles/73336; https://doaj.org/toc/2050-084X |
| DOI: | 10.7554/eLife.73336 |
| URL الوصول: | https://doaj.org/article/d5bc844519104cae8d3da4e41b6883b8 |
| رقم الأكسشن: | edsdoj.5bc844519104cae8d3da4e41b6883b8 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 2050084X |
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| DOI: | 10.7554/eLife.73336 |