Force Dependence of Proteins’ Transition State Position and the Bell–Evans Model

Single-molecule force spectroscopy has opened a new field of research in molecular biophysics and biochemistry. Pulling experiments on individual proteins permit us to monitor conformational transitions with high temporal resolution and measure their free energy landscape. The force–extension curves...

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Autores principales:	Marc Rico-Pasto, Annamaria Zaltron, Felix Ritort
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	single-molecule force spectroscopy protein folding free-energy landscape Bell–Evans model Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/60a415672b234cb6b866377221b85b32
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spelling	oai:doaj.org-article:60a415672b234cb6b866377221b85b322021-11-25T18:31:48ZForce Dependence of Proteins’ Transition State Position and the Bell–Evans Model10.3390/nano111130232079-4991https://doaj.org/article/60a415672b234cb6b866377221b85b322021-11-01T00:00:00Zhttps://www.mdpi.com/2079-4991/11/11/3023https://doaj.org/toc/2079-4991Single-molecule force spectroscopy has opened a new field of research in molecular biophysics and biochemistry. Pulling experiments on individual proteins permit us to monitor conformational transitions with high temporal resolution and measure their free energy landscape. The force–extension curves of single proteins often present large hysteresis, with unfolding forces that are higher than refolding ones. Therefore, the high energy of the transition state (TS) in these molecules precludes kinetic rates measurements in equilibrium hopping experiments. In irreversible pulling experiments, force-dependent kinetic rates measurements show a systematic discrepancy between the sum of the folding and unfolding TS distances derived by the kinetic Bell–Evans model and the full molecular extension predicted by elastic models. Here, we show that this discrepancy originates from the force-induced movement of TS. Specifically, we investigate the highly kinetically stable protein barnase, using pulling experiments and the Bell–Evans model to characterize the position of its kinetic barrier. Experimental results show that while the TS stays at a roughly constant distance relative to the native state, it shifts with force relative to the unfolded state. Interestingly, a conversion of the protein extension into amino acid units shows that the TS position follows the Leffler–Hammond postulate: the higher the force, the lower the number of unzipped amino acids relative to the native state. The results are compared with the quasi-reversible unfolding–folding of a short DNA hairpin.Marc Rico-PastoAnnamaria ZaltronFelix RitortMDPI AGarticlesingle-molecule force spectroscopyprotein foldingfree-energy landscapeBell–Evans modelChemistryQD1-999ENNanomaterials, Vol 11, Iss 3023, p 3023 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	single-molecule force spectroscopy protein folding free-energy landscape Bell–Evans model Chemistry QD1-999
spellingShingle	single-molecule force spectroscopy protein folding free-energy landscape Bell–Evans model Chemistry QD1-999 Marc Rico-Pasto Annamaria Zaltron Felix Ritort Force Dependence of Proteins’ Transition State Position and the Bell–Evans Model
description	Single-molecule force spectroscopy has opened a new field of research in molecular biophysics and biochemistry. Pulling experiments on individual proteins permit us to monitor conformational transitions with high temporal resolution and measure their free energy landscape. The force–extension curves of single proteins often present large hysteresis, with unfolding forces that are higher than refolding ones. Therefore, the high energy of the transition state (TS) in these molecules precludes kinetic rates measurements in equilibrium hopping experiments. In irreversible pulling experiments, force-dependent kinetic rates measurements show a systematic discrepancy between the sum of the folding and unfolding TS distances derived by the kinetic Bell–Evans model and the full molecular extension predicted by elastic models. Here, we show that this discrepancy originates from the force-induced movement of TS. Specifically, we investigate the highly kinetically stable protein barnase, using pulling experiments and the Bell–Evans model to characterize the position of its kinetic barrier. Experimental results show that while the TS stays at a roughly constant distance relative to the native state, it shifts with force relative to the unfolded state. Interestingly, a conversion of the protein extension into amino acid units shows that the TS position follows the Leffler–Hammond postulate: the higher the force, the lower the number of unzipped amino acids relative to the native state. The results are compared with the quasi-reversible unfolding–folding of a short DNA hairpin.
format	article
author	Marc Rico-Pasto Annamaria Zaltron Felix Ritort
author_facet	Marc Rico-Pasto Annamaria Zaltron Felix Ritort
author_sort	Marc Rico-Pasto
title	Force Dependence of Proteins’ Transition State Position and the Bell–Evans Model
title_short	Force Dependence of Proteins’ Transition State Position and the Bell–Evans Model
title_full	Force Dependence of Proteins’ Transition State Position and the Bell–Evans Model
title_fullStr	Force Dependence of Proteins’ Transition State Position and the Bell–Evans Model
title_full_unstemmed	Force Dependence of Proteins’ Transition State Position and the Bell–Evans Model
title_sort	force dependence of proteins’ transition state position and the bell–evans model
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/60a415672b234cb6b866377221b85b32
work_keys_str_mv	AT marcricopasto forcedependenceofproteinstransitionstatepositionandthebellevansmodel AT annamariazaltron forcedependenceofproteinstransitionstatepositionandthebellevansmodel AT felixritort forcedependenceofproteinstransitionstatepositionandthebellevansmodel
_version_	1718411019261313024

Force Dependence of Proteins’ Transition State Position and the Bell–Evans Model

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