Hsp70 chaperones are non-equilibrium machines that achieve ultra-affinity by energy consumption
70-kDa Heat shock proteins are ATP-driven molecular chaperones that perform a myriad of essential cellular tasks. Although structural and biochemical studies have shed some light on their functional mechanism, the fundamental issue of the role of energy consumption, due to ATP-hydrolysis, has remain...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2014-05-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/02218 |
| _version_ | 1828375638865608704 |
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| author | Paolo De Los Rios Alessandro Barducci |
| author_facet | Paolo De Los Rios Alessandro Barducci |
| author_sort | Paolo De Los Rios |
| collection | DOAJ |
| description | 70-kDa Heat shock proteins are ATP-driven molecular chaperones that perform a myriad of essential cellular tasks. Although structural and biochemical studies have shed some light on their functional mechanism, the fundamental issue of the role of energy consumption, due to ATP-hydrolysis, has remained unaddressed. Here we establish a clear connection between the non-equilibrium nature of Hsp70, due to ATP hydrolysis, and the determining feature of its function, namely its high affinity for its substrates. Energy consumption can indeed decrease the dissociation constant of the chaperone-substrate complex by several orders of magnitude with respect to an equilibrium scenario. We find that the biochemical requirements for observing such ultra-affinity coincide with the physiological conditions in the cell. Our results rationalize several experimental observations and pave the way for further analysis of non-equilibrium effects underlying chaperone functions. |
| first_indexed | 2024-04-14T07:49:16Z |
| format | Article |
| id | doaj.art-dc0deb9258054373a5d04b0a2104d90a |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:49:16Z |
| publishDate | 2014-05-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-dc0deb9258054373a5d04b0a2104d90a2022-12-22T02:05:14ZengeLife Sciences Publications LtdeLife2050-084X2014-05-01310.7554/eLife.02218Hsp70 chaperones are non-equilibrium machines that achieve ultra-affinity by energy consumptionPaolo De Los Rios0Alessandro Barducci1Laboratoire de Biophysique Statistique, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, SwitzerlandLaboratoire de Biophysique Statistique, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland70-kDa Heat shock proteins are ATP-driven molecular chaperones that perform a myriad of essential cellular tasks. Although structural and biochemical studies have shed some light on their functional mechanism, the fundamental issue of the role of energy consumption, due to ATP-hydrolysis, has remained unaddressed. Here we establish a clear connection between the non-equilibrium nature of Hsp70, due to ATP hydrolysis, and the determining feature of its function, namely its high affinity for its substrates. Energy consumption can indeed decrease the dissociation constant of the chaperone-substrate complex by several orders of magnitude with respect to an equilibrium scenario. We find that the biochemical requirements for observing such ultra-affinity coincide with the physiological conditions in the cell. Our results rationalize several experimental observations and pave the way for further analysis of non-equilibrium effects underlying chaperone functions.https://elifesciences.org/articles/02218chaperonenon-equilibriumdissociation constant |
| spellingShingle | Paolo De Los Rios Alessandro Barducci Hsp70 chaperones are non-equilibrium machines that achieve ultra-affinity by energy consumption eLife chaperone non-equilibrium dissociation constant |
| title | Hsp70 chaperones are non-equilibrium machines that achieve ultra-affinity by energy consumption |
| title_full | Hsp70 chaperones are non-equilibrium machines that achieve ultra-affinity by energy consumption |
| title_fullStr | Hsp70 chaperones are non-equilibrium machines that achieve ultra-affinity by energy consumption |
| title_full_unstemmed | Hsp70 chaperones are non-equilibrium machines that achieve ultra-affinity by energy consumption |
| title_short | Hsp70 chaperones are non-equilibrium machines that achieve ultra-affinity by energy consumption |
| title_sort | hsp70 chaperones are non equilibrium machines that achieve ultra affinity by energy consumption |
| topic | chaperone non-equilibrium dissociation constant |
| url | https://elifesciences.org/articles/02218 |
| work_keys_str_mv | AT paolodelosrios hsp70chaperonesarenonequilibriummachinesthatachieveultraaffinitybyenergyconsumption AT alessandrobarducci hsp70chaperonesarenonequilibriummachinesthatachieveultraaffinitybyenergyconsumption |