Dynamic prestress in a globular protein.

A protein at equilibrium is commonly thought of as a fully relaxed structure, with the intra-molecular interactions showing fluctuations around their energy minimum. In contrast, here we find direct evidence for a protein as a molecular tensegrity structure, comprising a balance of tensed and compre...

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Autores principales:	Scott A Edwards, Johannes Wagner, Frauke Gräter
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/345c28c4ba334b8bbc409e56947ba455
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spelling	oai:doaj.org-article:345c28c4ba334b8bbc409e56947ba4552021-11-18T05:51:20ZDynamic prestress in a globular protein.1553-734X1553-735810.1371/journal.pcbi.1002509https://doaj.org/article/345c28c4ba334b8bbc409e56947ba4552012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22589712/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358A protein at equilibrium is commonly thought of as a fully relaxed structure, with the intra-molecular interactions showing fluctuations around their energy minimum. In contrast, here we find direct evidence for a protein as a molecular tensegrity structure, comprising a balance of tensed and compressed interactions, a concept that has been put forward for macroscopic structures. We quantified the distribution of inter-residue prestress in ubiquitin and immunoglobulin from all-atom molecular dynamics simulations. The network of highly fluctuating yet significant inter-residue forces in proteins is a consequence of the intrinsic frustration of a protein when sampling its rugged energy landscape. In beta sheets, this balance of forces is found to compress the intra-strand hydrogen bonds. We estimate that the observed magnitude of this pre-compression is enough to induce significant changes in the hydrogen bond lifetimes; thus, prestress, which can be as high as a few 100 pN, can be considered a key factor in determining the unfolding kinetics and pathway of proteins under force. Strong pre-tension in certain salt bridges on the other hand is connected to the thermodynamic stability of ubiquitin. Effective force profiles between some side-chains reveal the signature of multiple, distinct conformational states, and such static disorder could be one factor explaining the growing body of experiments revealing non-exponential unfolding kinetics of proteins. The design of prestress distributions in engineering proteins promises to be a new tool for tailoring the mechanical properties of made-to-order nanomaterials.Scott A EdwardsJohannes WagnerFrauke GräterPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 8, Iss 5, p e1002509 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Scott A Edwards Johannes Wagner Frauke Gräter Dynamic prestress in a globular protein.
description	A protein at equilibrium is commonly thought of as a fully relaxed structure, with the intra-molecular interactions showing fluctuations around their energy minimum. In contrast, here we find direct evidence for a protein as a molecular tensegrity structure, comprising a balance of tensed and compressed interactions, a concept that has been put forward for macroscopic structures. We quantified the distribution of inter-residue prestress in ubiquitin and immunoglobulin from all-atom molecular dynamics simulations. The network of highly fluctuating yet significant inter-residue forces in proteins is a consequence of the intrinsic frustration of a protein when sampling its rugged energy landscape. In beta sheets, this balance of forces is found to compress the intra-strand hydrogen bonds. We estimate that the observed magnitude of this pre-compression is enough to induce significant changes in the hydrogen bond lifetimes; thus, prestress, which can be as high as a few 100 pN, can be considered a key factor in determining the unfolding kinetics and pathway of proteins under force. Strong pre-tension in certain salt bridges on the other hand is connected to the thermodynamic stability of ubiquitin. Effective force profiles between some side-chains reveal the signature of multiple, distinct conformational states, and such static disorder could be one factor explaining the growing body of experiments revealing non-exponential unfolding kinetics of proteins. The design of prestress distributions in engineering proteins promises to be a new tool for tailoring the mechanical properties of made-to-order nanomaterials.
format	article
author	Scott A Edwards Johannes Wagner Frauke Gräter
author_facet	Scott A Edwards Johannes Wagner Frauke Gräter
author_sort	Scott A Edwards
title	Dynamic prestress in a globular protein.
title_short	Dynamic prestress in a globular protein.
title_full	Dynamic prestress in a globular protein.
title_fullStr	Dynamic prestress in a globular protein.
title_full_unstemmed	Dynamic prestress in a globular protein.
title_sort	dynamic prestress in a globular protein.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/345c28c4ba334b8bbc409e56947ba455
work_keys_str_mv	AT scottaedwards dynamicprestressinaglobularprotein AT johanneswagner dynamicprestressinaglobularprotein AT fraukegrater dynamicprestressinaglobularprotein
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Dynamic prestress in a globular protein.

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