Structural transitions in orb2 prion-like domain relevant for functional aggregation in memory consolidation
Main Author: | |
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Publication Date: | 2020 |
Other Authors: | , , |
Format: | Article |
Language: | eng |
Source: | Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) |
Download full: | http://hdl.handle.net/10362/117153 |
Summary: | Grant BBM_TRA_0203 PD/BD/148028/2019 UIDB/04378/2020 |
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Structural transitions in orb2 prion-like domain relevant for functional aggregation in memory consolidationBiochemistryMolecular BiologyCell BiologyGrant BBM_TRA_0203 PD/BD/148028/2019 UIDB/04378/2020The recent structural elucidation of ex vivo Drosophila Orb2 fibrils revealed a novel amyloid formed by interdigitated Gln and His residue side chains belonging to the prion-like domain. However, atomic-level details on the conformational transitions associated with memory consolidation remain unknown. Here, we have characterized the nascent conformation and dynamics of the prion-like domain (PLD) of Orb2A using a nonconventional liquid-state NMR spectroscopy strategy based on 13C detection to afford an essentially complete set of 13Ca, 13Cb, 1Ha, and backbone 13CO and 15N assignments. At pH 4, where His residues are protonated, the PLD is disordered and flexible, except for a partially populated a-helix spanning residues 55–60, and binds RNA oligos, but not divalent cations. At pH 7, in contrast, His residues are predominantly neutral, and the Q/H segments adopt minor populations of helical structure, show decreased mobility and start to self-associate. At pH 7, the His residues do not bind RNA or Ca21, but do bind Zn21, which promotes further association. These findings represent a remarkable case of structural plasticity, based on which an updated model for Orb2A functional amyloidogenesis is suggested.DQ - Departamento de QuímicaUCIBIO - Applied Molecular Biosciences UnitRUNOroz, JavierFélix, Sara S.Cabrita, Eurico J.Laurents, Douglas V.2021-05-05T23:27:26Z2020-12-252020-12-25T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article12application/pdfhttp://hdl.handle.net/10362/117153eng0021-9258PURE: 28079093https://doi.org/10.1074/jbc.RA120.015211info:eu-repo/semantics/openAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2024-05-22T17:53:00Zoai:run.unl.pt:10362/117153Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-28T17:24:03.445374Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse |
dc.title.none.fl_str_mv |
Structural transitions in orb2 prion-like domain relevant for functional aggregation in memory consolidation |
title |
Structural transitions in orb2 prion-like domain relevant for functional aggregation in memory consolidation |
spellingShingle |
Structural transitions in orb2 prion-like domain relevant for functional aggregation in memory consolidation Oroz, Javier Biochemistry Molecular Biology Cell Biology |
title_short |
Structural transitions in orb2 prion-like domain relevant for functional aggregation in memory consolidation |
title_full |
Structural transitions in orb2 prion-like domain relevant for functional aggregation in memory consolidation |
title_fullStr |
Structural transitions in orb2 prion-like domain relevant for functional aggregation in memory consolidation |
title_full_unstemmed |
Structural transitions in orb2 prion-like domain relevant for functional aggregation in memory consolidation |
title_sort |
Structural transitions in orb2 prion-like domain relevant for functional aggregation in memory consolidation |
author |
Oroz, Javier |
author_facet |
Oroz, Javier Félix, Sara S. Cabrita, Eurico J. Laurents, Douglas V. |
author_role |
author |
author2 |
Félix, Sara S. Cabrita, Eurico J. Laurents, Douglas V. |
author2_role |
author author author |
dc.contributor.none.fl_str_mv |
DQ - Departamento de Química UCIBIO - Applied Molecular Biosciences Unit RUN |
dc.contributor.author.fl_str_mv |
Oroz, Javier Félix, Sara S. Cabrita, Eurico J. Laurents, Douglas V. |
dc.subject.por.fl_str_mv |
Biochemistry Molecular Biology Cell Biology |
topic |
Biochemistry Molecular Biology Cell Biology |
description |
Grant BBM_TRA_0203 PD/BD/148028/2019 UIDB/04378/2020 |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-12-25 2020-12-25T00:00:00Z 2021-05-05T23:27:26Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10362/117153 |
url |
http://hdl.handle.net/10362/117153 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
0021-9258 PURE: 28079093 https://doi.org/10.1074/jbc.RA120.015211 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
12 application/pdf |
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Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) |
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Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) |
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Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia |
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info@rcaap.pt |
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