Characterization of the structural forces governing the reversibility of the thermal unfolding of the human acidic fibroblast growth factor

Abstract Human acidic fibroblast growth factor (hFGF1) is an all beta-sheet protein that is involved in the regulation of key cellular processes including cell proliferation and wound healing. hFGF1 is known to aggregate when subjected to thermal unfolding. In this study, we investigate the equilibr...

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Autores principales:	Shilpi Agrawal, Vivek Govind Kumar, Ravi Kumar Gundampati, Mahmoud Moradi, Thallapuranam Krishnaswamy Suresh Kumar
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/005e77758849402eabcccf23b28c49d7
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spelling	oai:doaj.org-article:005e77758849402eabcccf23b28c49d72021-12-02T17:06:33ZCharacterization of the structural forces governing the reversibility of the thermal unfolding of the human acidic fibroblast growth factor10.1038/s41598-021-95050-22045-2322https://doaj.org/article/005e77758849402eabcccf23b28c49d72021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95050-2https://doaj.org/toc/2045-2322Abstract Human acidic fibroblast growth factor (hFGF1) is an all beta-sheet protein that is involved in the regulation of key cellular processes including cell proliferation and wound healing. hFGF1 is known to aggregate when subjected to thermal unfolding. In this study, we investigate the equilibrium unfolding of hFGF1 using a wide array of biophysical and biochemical techniques. Systematic analyses of the thermal and chemical denaturation data on hFGF1 variants (Q54P, K126N, R136E, K126N/R136E, Q54P/K126N, Q54P/R136E, and Q54P/K126N/R136E) indicate that nullification of charges in the heparin-binding pocket can significantly increase the stability of wtFGF1. Triple variant (Q54P/K126N/R136E) was found to be the most stable of all the hFGF1 variants studied. With the exception of triple variant, thermal unfolding of wtFGF1 and the other variants is irreversible. Thermally unfolded triple variant refolds completely to its biologically native conformation. Microsecond-level molecular dynamic simulations reveal that a network of hydrogen bonds and salt bridges linked to Q54P, K126N, and R136E mutations, are responsible for the high stability and reversibility of thermal unfolding of the triple variant. In our opinion, the findings of the study provide valuable clues for the rational design of a stable hFGF1 variant that exhibits potent wound healing properties.Shilpi AgrawalVivek Govind KumarRavi Kumar GundampatiMahmoud MoradiThallapuranam Krishnaswamy Suresh KumarNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shilpi Agrawal Vivek Govind Kumar Ravi Kumar Gundampati Mahmoud Moradi Thallapuranam Krishnaswamy Suresh Kumar Characterization of the structural forces governing the reversibility of the thermal unfolding of the human acidic fibroblast growth factor
description	Abstract Human acidic fibroblast growth factor (hFGF1) is an all beta-sheet protein that is involved in the regulation of key cellular processes including cell proliferation and wound healing. hFGF1 is known to aggregate when subjected to thermal unfolding. In this study, we investigate the equilibrium unfolding of hFGF1 using a wide array of biophysical and biochemical techniques. Systematic analyses of the thermal and chemical denaturation data on hFGF1 variants (Q54P, K126N, R136E, K126N/R136E, Q54P/K126N, Q54P/R136E, and Q54P/K126N/R136E) indicate that nullification of charges in the heparin-binding pocket can significantly increase the stability of wtFGF1. Triple variant (Q54P/K126N/R136E) was found to be the most stable of all the hFGF1 variants studied. With the exception of triple variant, thermal unfolding of wtFGF1 and the other variants is irreversible. Thermally unfolded triple variant refolds completely to its biologically native conformation. Microsecond-level molecular dynamic simulations reveal that a network of hydrogen bonds and salt bridges linked to Q54P, K126N, and R136E mutations, are responsible for the high stability and reversibility of thermal unfolding of the triple variant. In our opinion, the findings of the study provide valuable clues for the rational design of a stable hFGF1 variant that exhibits potent wound healing properties.
format	article
author	Shilpi Agrawal Vivek Govind Kumar Ravi Kumar Gundampati Mahmoud Moradi Thallapuranam Krishnaswamy Suresh Kumar
author_facet	Shilpi Agrawal Vivek Govind Kumar Ravi Kumar Gundampati Mahmoud Moradi Thallapuranam Krishnaswamy Suresh Kumar
author_sort	Shilpi Agrawal
title	Characterization of the structural forces governing the reversibility of the thermal unfolding of the human acidic fibroblast growth factor
title_short	Characterization of the structural forces governing the reversibility of the thermal unfolding of the human acidic fibroblast growth factor
title_full	Characterization of the structural forces governing the reversibility of the thermal unfolding of the human acidic fibroblast growth factor
title_fullStr	Characterization of the structural forces governing the reversibility of the thermal unfolding of the human acidic fibroblast growth factor
title_full_unstemmed	Characterization of the structural forces governing the reversibility of the thermal unfolding of the human acidic fibroblast growth factor
title_sort	characterization of the structural forces governing the reversibility of the thermal unfolding of the human acidic fibroblast growth factor
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/005e77758849402eabcccf23b28c49d7
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Characterization of the structural forces governing the reversibility of the thermal unfolding of the human acidic fibroblast growth factor

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