Protein residue network analysis reveals fundamental properties of the human coagulation factor VIII

Abstract Hemophilia A is an X-linked inherited blood coagulation disorder caused by the production and circulation of defective coagulation factor VIII protein. People living with this condition receive either prophylaxis or on-demand treatment, and approximately 30% of patients develop inhibitor an...

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Autores principales:	Tiago J. S. Lopes, Ricardo Rios, Tatiane Nogueira, Rodrigo F. Mello
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/463b9a2b09e6452aa5dfb631fb3f159b
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spelling	oai:doaj.org-article:463b9a2b09e6452aa5dfb631fb3f159b2021-12-02T17:40:45ZProtein residue network analysis reveals fundamental properties of the human coagulation factor VIII10.1038/s41598-021-92201-32045-2322https://doaj.org/article/463b9a2b09e6452aa5dfb631fb3f159b2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92201-3https://doaj.org/toc/2045-2322Abstract Hemophilia A is an X-linked inherited blood coagulation disorder caused by the production and circulation of defective coagulation factor VIII protein. People living with this condition receive either prophylaxis or on-demand treatment, and approximately 30% of patients develop inhibitor antibodies, a serious complication that limits treatment options. Although previous studies performed targeted mutations to identify important residues of FVIII, a detailed understanding of the role of each amino acid and their neighboring residues is still lacking. Here, we addressed this issue by creating a residue interaction network (RIN) where the nodes are the FVIII residues, and two nodes are connected if their corresponding residues are in close proximity in the FVIII protein structure. We studied the characteristics of all residues in this network and found important properties related to disease severity, interaction to other proteins and structural stability. Importantly, we found that the RIN-derived properties were in close agreement with in vitro and clinical reports, corroborating the observation that the patterns derived from this detailed map of the FVIII protein architecture accurately capture the biological properties of FVIII.Tiago J. S. LopesRicardo RiosTatiane NogueiraRodrigo F. MelloNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tiago J. S. Lopes Ricardo Rios Tatiane Nogueira Rodrigo F. Mello Protein residue network analysis reveals fundamental properties of the human coagulation factor VIII
description	Abstract Hemophilia A is an X-linked inherited blood coagulation disorder caused by the production and circulation of defective coagulation factor VIII protein. People living with this condition receive either prophylaxis or on-demand treatment, and approximately 30% of patients develop inhibitor antibodies, a serious complication that limits treatment options. Although previous studies performed targeted mutations to identify important residues of FVIII, a detailed understanding of the role of each amino acid and their neighboring residues is still lacking. Here, we addressed this issue by creating a residue interaction network (RIN) where the nodes are the FVIII residues, and two nodes are connected if their corresponding residues are in close proximity in the FVIII protein structure. We studied the characteristics of all residues in this network and found important properties related to disease severity, interaction to other proteins and structural stability. Importantly, we found that the RIN-derived properties were in close agreement with in vitro and clinical reports, corroborating the observation that the patterns derived from this detailed map of the FVIII protein architecture accurately capture the biological properties of FVIII.
format	article
author	Tiago J. S. Lopes Ricardo Rios Tatiane Nogueira Rodrigo F. Mello
author_facet	Tiago J. S. Lopes Ricardo Rios Tatiane Nogueira Rodrigo F. Mello
author_sort	Tiago J. S. Lopes
title	Protein residue network analysis reveals fundamental properties of the human coagulation factor VIII
title_short	Protein residue network analysis reveals fundamental properties of the human coagulation factor VIII
title_full	Protein residue network analysis reveals fundamental properties of the human coagulation factor VIII
title_fullStr	Protein residue network analysis reveals fundamental properties of the human coagulation factor VIII
title_full_unstemmed	Protein residue network analysis reveals fundamental properties of the human coagulation factor VIII
title_sort	protein residue network analysis reveals fundamental properties of the human coagulation factor viii
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/463b9a2b09e6452aa5dfb631fb3f159b
work_keys_str_mv	AT tiagojslopes proteinresiduenetworkanalysisrevealsfundamentalpropertiesofthehumancoagulationfactorviii AT ricardorios proteinresiduenetworkanalysisrevealsfundamentalpropertiesofthehumancoagulationfactorviii AT tatianenogueira proteinresiduenetworkanalysisrevealsfundamentalpropertiesofthehumancoagulationfactorviii AT rodrigofmello proteinresiduenetworkanalysisrevealsfundamentalpropertiesofthehumancoagulationfactorviii
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Protein residue network analysis reveals fundamental properties of the human coagulation factor VIII

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