Identification of proteins that specifically recognize and bind protofibrillar aggregates of amyloid-β

Abstract Protofibrils of the 42 amino acids long amyloid-β peptide are transient pre-fibrillar intermediates in the process of peptide aggregation into amyloid plaques and are thought to play a critical role in the pathology of Alzheimer’s disease. Hence, there is a need for research reagents and po...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Elisabet Wahlberg, M. Mahafuzur Rahman, Hanna Lindberg, Elin Gunneriusson, Benjamin Schmuck, Christofer Lendel, Mats Sandgren, John Löfblom, Stefan Ståhl, Torleif Härd
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/043cb248dd84408f9df468ef7c517166
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:043cb248dd84408f9df468ef7c517166
record_format	dspace
spelling	oai:doaj.org-article:043cb248dd84408f9df468ef7c5171662021-12-02T12:32:16ZIdentification of proteins that specifically recognize and bind protofibrillar aggregates of amyloid-β10.1038/s41598-017-06377-82045-2322https://doaj.org/article/043cb248dd84408f9df468ef7c5171662017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06377-8https://doaj.org/toc/2045-2322Abstract Protofibrils of the 42 amino acids long amyloid-β peptide are transient pre-fibrillar intermediates in the process of peptide aggregation into amyloid plaques and are thought to play a critical role in the pathology of Alzheimer’s disease. Hence, there is a need for research reagents and potential diagnostic reagents for detection and imaging of such aggregates. Here we describe an in vitro selection of Affibody molecules that bind to protofibrils of Aβ42cc, which is a stable engineered mimic of wild type Aβ42 protofibrils. Several binders were identified that bind Aβ42cc protofibrils with low nanomolar affinities, and which also recognize wild type Aβ42 protofibrils. Dimeric head-to-tail fusion proteins with subnanomolar binding affinities, and very slow dissociation off-rates, were also constructed. A mapping of the chemical properties of the side chains onto the Affibody scaffold surface reveals three distinct adjacent surface areas of positively charged surface, nonpolar surface and a polar surface, which presumably match a corresponding surface epitope on the protofibrils. The results demonstrate that the engineered Aβ42cc is a suitable antigen for directed evolution of affinity reagents with specificity for wild type Aβ42 protofibrils.Elisabet WahlbergM. Mahafuzur RahmanHanna LindbergElin GunneriussonBenjamin SchmuckChristofer LendelMats SandgrenJohn LöfblomStefan StåhlTorleif HärdNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Elisabet Wahlberg M. Mahafuzur Rahman Hanna Lindberg Elin Gunneriusson Benjamin Schmuck Christofer Lendel Mats Sandgren John Löfblom Stefan Ståhl Torleif Härd Identification of proteins that specifically recognize and bind protofibrillar aggregates of amyloid-β
description	Abstract Protofibrils of the 42 amino acids long amyloid-β peptide are transient pre-fibrillar intermediates in the process of peptide aggregation into amyloid plaques and are thought to play a critical role in the pathology of Alzheimer’s disease. Hence, there is a need for research reagents and potential diagnostic reagents for detection and imaging of such aggregates. Here we describe an in vitro selection of Affibody molecules that bind to protofibrils of Aβ42cc, which is a stable engineered mimic of wild type Aβ42 protofibrils. Several binders were identified that bind Aβ42cc protofibrils with low nanomolar affinities, and which also recognize wild type Aβ42 protofibrils. Dimeric head-to-tail fusion proteins with subnanomolar binding affinities, and very slow dissociation off-rates, were also constructed. A mapping of the chemical properties of the side chains onto the Affibody scaffold surface reveals three distinct adjacent surface areas of positively charged surface, nonpolar surface and a polar surface, which presumably match a corresponding surface epitope on the protofibrils. The results demonstrate that the engineered Aβ42cc is a suitable antigen for directed evolution of affinity reagents with specificity for wild type Aβ42 protofibrils.
format	article
author	Elisabet Wahlberg M. Mahafuzur Rahman Hanna Lindberg Elin Gunneriusson Benjamin Schmuck Christofer Lendel Mats Sandgren John Löfblom Stefan Ståhl Torleif Härd
author_facet	Elisabet Wahlberg M. Mahafuzur Rahman Hanna Lindberg Elin Gunneriusson Benjamin Schmuck Christofer Lendel Mats Sandgren John Löfblom Stefan Ståhl Torleif Härd
author_sort	Elisabet Wahlberg
title	Identification of proteins that specifically recognize and bind protofibrillar aggregates of amyloid-β
title_short	Identification of proteins that specifically recognize and bind protofibrillar aggregates of amyloid-β
title_full	Identification of proteins that specifically recognize and bind protofibrillar aggregates of amyloid-β
title_fullStr	Identification of proteins that specifically recognize and bind protofibrillar aggregates of amyloid-β
title_full_unstemmed	Identification of proteins that specifically recognize and bind protofibrillar aggregates of amyloid-β
title_sort	identification of proteins that specifically recognize and bind protofibrillar aggregates of amyloid-β
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/043cb248dd84408f9df468ef7c517166
work_keys_str_mv	AT elisabetwahlberg identificationofproteinsthatspecificallyrecognizeandbindprotofibrillaraggregatesofamyloidb AT mmahafuzurrahman identificationofproteinsthatspecificallyrecognizeandbindprotofibrillaraggregatesofamyloidb AT hannalindberg identificationofproteinsthatspecificallyrecognizeandbindprotofibrillaraggregatesofamyloidb AT elingunneriusson identificationofproteinsthatspecificallyrecognizeandbindprotofibrillaraggregatesofamyloidb AT benjaminschmuck identificationofproteinsthatspecificallyrecognizeandbindprotofibrillaraggregatesofamyloidb AT christoferlendel identificationofproteinsthatspecificallyrecognizeandbindprotofibrillaraggregatesofamyloidb AT matssandgren identificationofproteinsthatspecificallyrecognizeandbindprotofibrillaraggregatesofamyloidb AT johnlofblom identificationofproteinsthatspecificallyrecognizeandbindprotofibrillaraggregatesofamyloidb AT stefanstahl identificationofproteinsthatspecificallyrecognizeandbindprotofibrillaraggregatesofamyloidb AT torleifhard identificationofproteinsthatspecificallyrecognizeandbindprotofibrillaraggregatesofamyloidb
_version_	1718394076947021824

Identification of proteins that specifically recognize and bind protofibrillar aggregates of amyloid-β

Ejemplares similares