Somatostatin, an in vivo binder to Aβ oligomers, Binds to βPFOAβ(1−42) Tetramers

Somatostatin (SST14) is strongly related to Alzheimer's disease (AD), as its levels decline during aging, it regulates the proteolytic degradation of the amyloid beta peptide (Aβ), and it binds to Aβ oligomers in vivo. Recently, the 3D structure of a membrane-associated β-sheet pore-forming tet...

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Detalles Bibliográficos
Autores: Puig Gomà-Camps, Eduard, Tolchard, James, Riera i Escalé, Antoni, Carulla Casanovas, Natàlia
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2020
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/172183
Acceso en línea:https://hdl.handle.net/2445/172183
Access Level:acceso abierto
Palabra clave:Malaltia d'Alzheimer
Oligòmers
Alzheimer's disease
Oligomers
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repository_id_str
spelling Somatostatin, an in vivo binder to Aβ oligomers, Binds to βPFOAβ(1−42) TetramersPuig Gomà-Camps, EduardTolchard, JamesRiera i Escalé, AntoniCarulla Casanovas, NatàliaMalaltia d'AlzheimerOligòmersAlzheimer's diseaseOligomersSomatostatin (SST14) is strongly related to Alzheimer's disease (AD), as its levels decline during aging, it regulates the proteolytic degradation of the amyloid beta peptide (Aβ), and it binds to Aβ oligomers in vivo. Recently, the 3D structure of a membrane-associated β-sheet pore-forming tetramer (βPFOAβ(1−42) tetramer) has been reported. Here, we show that SST14 binds selectively to the βPFOAβ(1−42) tetramer with a KD value of ∼40 μM without binding to monomeric Aβ(1−42). Specific NMR chemical shift perturbations, observed during titration of SST14, define a binding site in the βPFOAβ(1−42) tetramer and are in agreement with a 2:1 stoichiometry determined by both native mass spectroscopy and isothermal titration calorimetry. These results enabled us to perform driven docking and model the binding mode for the interaction. The present study provides additional evidence on the relation between SST14 and the amyloid cascade and positions the βPFOAβ(1−42) tetramer as a relevant aggregation form of Aβ and as a potential target for AD.American Chemical Society2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/2445/172183Articles publicats en revistes (Química Inorgànica i Orgànica)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésVersió postprint del document publicat a: https://doi.org/10.1021/acschemneuro.0c00470Acs Chemical Neuroscience, 2020, vol. 11, num. 20, p. 3358-3365https://doi.org/10.1021/acschemneuro.0c00470(c) American Chemical Society , 2020info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1721832026-05-27T06:46:51Z
dc.title.none.fl_str_mv Somatostatin, an in vivo binder to Aβ oligomers, Binds to βPFOAβ(1−42) Tetramers
title Somatostatin, an in vivo binder to Aβ oligomers, Binds to βPFOAβ(1−42) Tetramers
spellingShingle Somatostatin, an in vivo binder to Aβ oligomers, Binds to βPFOAβ(1−42) Tetramers
Puig Gomà-Camps, Eduard
Malaltia d'Alzheimer
Oligòmers
Alzheimer's disease
Oligomers
title_short Somatostatin, an in vivo binder to Aβ oligomers, Binds to βPFOAβ(1−42) Tetramers
title_full Somatostatin, an in vivo binder to Aβ oligomers, Binds to βPFOAβ(1−42) Tetramers
title_fullStr Somatostatin, an in vivo binder to Aβ oligomers, Binds to βPFOAβ(1−42) Tetramers
title_full_unstemmed Somatostatin, an in vivo binder to Aβ oligomers, Binds to βPFOAβ(1−42) Tetramers
title_sort Somatostatin, an in vivo binder to Aβ oligomers, Binds to βPFOAβ(1−42) Tetramers
dc.creator.none.fl_str_mv Puig Gomà-Camps, Eduard
Tolchard, James
Riera i Escalé, Antoni
Carulla Casanovas, Natàlia
author Puig Gomà-Camps, Eduard
author_facet Puig Gomà-Camps, Eduard
Tolchard, James
Riera i Escalé, Antoni
Carulla Casanovas, Natàlia
author_role author
author2 Tolchard, James
Riera i Escalé, Antoni
Carulla Casanovas, Natàlia
author2_role author
author
author
dc.subject.none.fl_str_mv Malaltia d'Alzheimer
Oligòmers
Alzheimer's disease
Oligomers
topic Malaltia d'Alzheimer
Oligòmers
Alzheimer's disease
Oligomers
description Somatostatin (SST14) is strongly related to Alzheimer's disease (AD), as its levels decline during aging, it regulates the proteolytic degradation of the amyloid beta peptide (Aβ), and it binds to Aβ oligomers in vivo. Recently, the 3D structure of a membrane-associated β-sheet pore-forming tetramer (βPFOAβ(1−42) tetramer) has been reported. Here, we show that SST14 binds selectively to the βPFOAβ(1−42) tetramer with a KD value of ∼40 μM without binding to monomeric Aβ(1−42). Specific NMR chemical shift perturbations, observed during titration of SST14, define a binding site in the βPFOAβ(1−42) tetramer and are in agreement with a 2:1 stoichiometry determined by both native mass spectroscopy and isothermal titration calorimetry. These results enabled us to perform driven docking and model the binding mode for the interaction. The present study provides additional evidence on the relation between SST14 and the amyloid cascade and positions the βPFOAβ(1−42) tetramer as a relevant aggregation form of Aβ and as a potential target for AD.
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/172183
url https://hdl.handle.net/2445/172183
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: https://doi.org/10.1021/acschemneuro.0c00470
Acs Chemical Neuroscience, 2020, vol. 11, num. 20, p. 3358-3365
https://doi.org/10.1021/acschemneuro.0c00470
dc.rights.none.fl_str_mv (c) American Chemical Society , 2020
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) American Chemical Society , 2020
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Chemical Society
publisher.none.fl_str_mv American Chemical Society
dc.source.none.fl_str_mv Articles publicats en revistes (Química Inorgànica i Orgànica)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300724

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