Peptides derived from MARCKS block coagulation complex assembly on phosphatidylserine

Abstract Blood coagulation involves activation of platelets and coagulation factors. At the interface of these two processes resides the lipid phosphatidylserine. Activated platelets expose phosphatidylserine on their outer membrane leaflet and activated clotting factors assemble into enzymatically...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Noah Kastelowitz, Ryo Tamura, Abimbola Onasoga, Timothy J. Stalker, Ormacinda R. White, Peter N. Brown, Gary L. Brodsky, Lawrence F. Brass, Brian R. Branchford, Jorge Di Paola, Hang Yin
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8ea431767bab459eae1b68e2da79914e
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:8ea431767bab459eae1b68e2da79914e
record_format	dspace
spelling	oai:doaj.org-article:8ea431767bab459eae1b68e2da79914e2021-12-02T16:07:46ZPeptides derived from MARCKS block coagulation complex assembly on phosphatidylserine10.1038/s41598-017-04494-y2045-2322https://doaj.org/article/8ea431767bab459eae1b68e2da79914e2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04494-yhttps://doaj.org/toc/2045-2322Abstract Blood coagulation involves activation of platelets and coagulation factors. At the interface of these two processes resides the lipid phosphatidylserine. Activated platelets expose phosphatidylserine on their outer membrane leaflet and activated clotting factors assemble into enzymatically active complexes on the exposed lipid, ultimately leading to the formation of fibrin. Here, we describe how small peptide and peptidomimetic probes derived from the lipid binding domain of the protein myristoylated alanine-rich C-kinase substrate (MARCKS) bind to phosphatidylserine exposed on activated platelets and thereby inhibit fibrin formation. The MARCKS peptides antagonize the binding of factor Xa to phosphatidylserine and inhibit the enzymatic activity of prothrombinase. In whole blood under flow, the MARCKS peptides colocalize with, and inhibit fibrin cross-linking, of adherent platelets. In vivo, we find that the MARCKS peptides circulate to remote injuries and bind to activated platelets in the inner core of developing thrombi.Noah KastelowitzRyo TamuraAbimbola OnasogaTimothy J. StalkerOrmacinda R. WhitePeter N. BrownGary L. BrodskyLawrence F. BrassBrian R. BranchfordJorge Di PaolaHang YinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Noah Kastelowitz Ryo Tamura Abimbola Onasoga Timothy J. Stalker Ormacinda R. White Peter N. Brown Gary L. Brodsky Lawrence F. Brass Brian R. Branchford Jorge Di Paola Hang Yin Peptides derived from MARCKS block coagulation complex assembly on phosphatidylserine
description	Abstract Blood coagulation involves activation of platelets and coagulation factors. At the interface of these two processes resides the lipid phosphatidylserine. Activated platelets expose phosphatidylserine on their outer membrane leaflet and activated clotting factors assemble into enzymatically active complexes on the exposed lipid, ultimately leading to the formation of fibrin. Here, we describe how small peptide and peptidomimetic probes derived from the lipid binding domain of the protein myristoylated alanine-rich C-kinase substrate (MARCKS) bind to phosphatidylserine exposed on activated platelets and thereby inhibit fibrin formation. The MARCKS peptides antagonize the binding of factor Xa to phosphatidylserine and inhibit the enzymatic activity of prothrombinase. In whole blood under flow, the MARCKS peptides colocalize with, and inhibit fibrin cross-linking, of adherent platelets. In vivo, we find that the MARCKS peptides circulate to remote injuries and bind to activated platelets in the inner core of developing thrombi.
format	article
author	Noah Kastelowitz Ryo Tamura Abimbola Onasoga Timothy J. Stalker Ormacinda R. White Peter N. Brown Gary L. Brodsky Lawrence F. Brass Brian R. Branchford Jorge Di Paola Hang Yin
author_facet	Noah Kastelowitz Ryo Tamura Abimbola Onasoga Timothy J. Stalker Ormacinda R. White Peter N. Brown Gary L. Brodsky Lawrence F. Brass Brian R. Branchford Jorge Di Paola Hang Yin
author_sort	Noah Kastelowitz
title	Peptides derived from MARCKS block coagulation complex assembly on phosphatidylserine
title_short	Peptides derived from MARCKS block coagulation complex assembly on phosphatidylserine
title_full	Peptides derived from MARCKS block coagulation complex assembly on phosphatidylserine
title_fullStr	Peptides derived from MARCKS block coagulation complex assembly on phosphatidylserine
title_full_unstemmed	Peptides derived from MARCKS block coagulation complex assembly on phosphatidylserine
title_sort	peptides derived from marcks block coagulation complex assembly on phosphatidylserine
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/8ea431767bab459eae1b68e2da79914e
work_keys_str_mv	AT noahkastelowitz peptidesderivedfrommarcksblockcoagulationcomplexassemblyonphosphatidylserine AT ryotamura peptidesderivedfrommarcksblockcoagulationcomplexassemblyonphosphatidylserine AT abimbolaonasoga peptidesderivedfrommarcksblockcoagulationcomplexassemblyonphosphatidylserine AT timothyjstalker peptidesderivedfrommarcksblockcoagulationcomplexassemblyonphosphatidylserine AT ormacindarwhite peptidesderivedfrommarcksblockcoagulationcomplexassemblyonphosphatidylserine AT peternbrown peptidesderivedfrommarcksblockcoagulationcomplexassemblyonphosphatidylserine AT garylbrodsky peptidesderivedfrommarcksblockcoagulationcomplexassemblyonphosphatidylserine AT lawrencefbrass peptidesderivedfrommarcksblockcoagulationcomplexassemblyonphosphatidylserine AT brianrbranchford peptidesderivedfrommarcksblockcoagulationcomplexassemblyonphosphatidylserine AT jorgedipaola peptidesderivedfrommarcksblockcoagulationcomplexassemblyonphosphatidylserine AT hangyin peptidesderivedfrommarcksblockcoagulationcomplexassemblyonphosphatidylserine
_version_	1718384729683656704

Peptides derived from MARCKS block coagulation complex assembly on phosphatidylserine

Ejemplares similares