Hierarchical dynamics in allostery following ATP hydrolysis monitored by single molecule FRET measurements and MD simulations
| العنوان: | Hierarchical dynamics in allostery following ATP hydrolysis monitored by single molecule FRET measurements and MD simulations |
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| المؤلفون: | Thorsten Hugel, Steffen Wolf, Gerhard Stock, Björn Hellenkamp, Johann Thurn, Benedikt Sohmen |
| المصدر: | Chemical Science |
| بيانات النشر: | Royal Society of Chemistry (RSC), 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0303 health sciences, Conformational change, biology, Chemistry, Allosteric regulation, General Chemistry, Single-molecule FRET, Folding (chemistry), 03 medical and health sciences, Molecular dynamics, 0302 clinical medicine, ATP hydrolysis, Chaperone (protein), biology.protein, Biophysics, Binding site, 030217 neurology & neurosurgery, 030304 developmental biology |
| الوصف: | We report on a study that combines advanced fluorescence methods with molecular dynamics (MD) simulations to cover timescales from nanoseconds to milliseconds for a large protein. This allows us to delineate how ATP hydrolysis in a protein causes allosteric changes at a distant protein binding site, using the chaperone Hsp90 as test system. The allosteric process occurs via hierarchical dynamics involving timescales from nano- to milliseconds and length scales from Ångstroms to several nanometers. We find that hydrolysis of one ATP is coupled to a conformational change of Arg380, which in turn passes structural information via the large M-domain α-helix to the whole protein. The resulting structural asymmetry in Hsp90 leads to the collapse of a central folding substrate binding site, causing the formation of a novel collapsed state (closed state B) that we characterise structurally. We presume that similar hierarchical mechanisms are fundamental for information transfer induced by ATP hydrolysis through many other proteins. We report on a study that combines advanced fluorescence methods with molecular dynamics simulations to cover timescales from nanoseconds to milliseconds for a large protein, the chaperone Hsp90. |
| تدمد: | 2041-6539 2041-6520 |
| DOI: | 10.1039/d0sc06134d |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2cdf03fa0fc987d463682ead6f940b06 https://doi.org/10.1039/d0sc06134d |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2cdf03fa0fc987d463682ead6f940b06 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20416539 20416520 |
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| DOI: | 10.1039/d0sc06134d |