Molecular coevolution of coagulation factor VIII and von Willebrand factor.

Animals Factor VIII / genetics Hemostasis von Willebrand Factor / genetics

Journal

Blood advances
ISSN: 2473-9537
Titre abrégé: Blood Adv
Pays: United States
ID NLM: 101698425

Informations de publication

Date de publication:
09 02 2021
Historique:
received: 16 07 2020
accepted: 09 12 2020
entrez: 9 2 2021
pubmed: 10 2 2021
medline: 29 5 2021
Statut: ppublish

Résumé

Ancestral sequence reconstruction provides a unique platform for investigating the molecular evolution of single gene products and recently has shown success in engineering advanced biological therapeutics. To date, the coevolution of proteins within complexes and protein-protein interactions is mostly investigated in silico via proteomics and/or within single-celled systems. Herein, ancestral sequence reconstruction is used to investigate the molecular evolution of 2 proteins linked not only by stabilizing association in circulation but also by their independent roles within the primary and secondary hemostatic systems of mammals. Using sequence analysis and biochemical characterization of recombinant ancestral von Willebrand factor (VWF) and coagulation factor VIII (FVIII), we investigated the evolution of the essential macromolecular FVIII/VWF complex. Our data support the hypothesis that these coagulation proteins coevolved throughout mammalian diversification, maintaining strong binding affinities while modulating independent and distinct hemostatic activities in diverse lineages.

Identifiants

DOI: 10.1182/bloodadvances.2020002971 PMID: 33560395 PMC: PMC7876868
pubmed: 33560395
pii: S2473-9529(21)00108-7
doi: 10.1182/bloodadvances.2020002971
pmc: PMC7876868
doi:

Substances chimiques

von Willebrand Factor 0
Factor VIII 9001-27-8

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

812-822

Subventions

Organisme : NIAMS NIH HHS
ID : R01 AR069137
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL137128
Pays : United States
Organisme : CIHR
ID : FDN154285
Pays : Canada

Informations de copyright

© 2021 by The American Society of Hematology.

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Auteurs

Philip M Zakas (PM)

Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada.

Christopher W Coyle (CW)

Program in Molecular and Systems Pharmacology, Laney Graduate School, Emory University, Atlanta, GA.

Anja Brehm (A)

Octapharma Biopharmaceuticals GmbH, Molecular Biochemistry, Berlin, Germany.

Marion Bayer (M)

Octapharma Biopharmaceuticals GmbH, Molecular Biochemistry, Berlin, Germany.

Barbara Solecka-Witulska (B)

Octapharma Biopharmaceuticals GmbH, Molecular Biochemistry, Berlin, Germany.

Caelan E Radford (CE)

School of Biological Sciences, Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA; and.

Christine Brown (C)

Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada.

Kate Nesbitt (K)

Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada.

Courtney Dwyer (C)

Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada.

Christoph Kannicht (C)

Octapharma Biopharmaceuticals GmbH, Molecular Biochemistry, Berlin, Germany.

H Trent Spencer (HT)

Program in Molecular and Systems Pharmacology, Laney Graduate School, Emory University, Atlanta, GA.
Aflac Cancer and Blood Disorders Center, Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA.

Eric A Gaucher (EA)

School of Biological Sciences, Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA; and.

Christopher B Doering (CB)

Program in Molecular and Systems Pharmacology, Laney Graduate School, Emory University, Atlanta, GA.
Aflac Cancer and Blood Disorders Center, Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA.

David Lillicrap (D)

Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Molecular coevolution of coagulation factor...
questionsmedicales.fr › Facteurs biologiques › Facteurs de la coagulation sanguine › Facteur VIII › Molecular coevolution of coagulation factor...
questionsmedicales.fr › Phénomènes physiologiques respiratoires et circulatoires › Phénomènes physiogiques du sang › Hémostase › Molecular coevolution of coagulation factor...
questionsmedicales.fr › Facteurs biologiques › Facteurs de la coagulation sanguine › Facteur de von Willebrand › Molecular coevolution of coagulation factor...