Cargando…

Acidic pH Promotes Refolding and Macroscopic Assembly of Amyloid β (16–22) Peptides at the Air–Water Interface

[Image: see text] Assembly by amyloid-beta (Aβ) peptides is vital for various neurodegenerative diseases. The process can be accelerated by hydrophobic interfaces such as the cell membrane interface and the air–water interface. Elucidating the assembly mechanism for Aβ peptides at hydrophobic interf...

Descripción completa

Detalles Bibliográficos
Autores principales: Lu, Hao, Bellucci, Luca, Sun, Shumei, Qi, Daizong, Rosa, Marta, Berger, Rüdiger, Corni, Stefano, Bonn, Mischa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2022
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9340808/
https://www.ncbi.nlm.nih.gov/pubmed/35839425
http://dx.doi.org/10.1021/acs.jpclett.2c01171
_version_ 1784760475223851008
author Lu, Hao
Bellucci, Luca
Sun, Shumei
Qi, Daizong
Rosa, Marta
Berger, Rüdiger
Corni, Stefano
Bonn, Mischa
author_facet Lu, Hao
Bellucci, Luca
Sun, Shumei
Qi, Daizong
Rosa, Marta
Berger, Rüdiger
Corni, Stefano
Bonn, Mischa
author_sort Lu, Hao
collection PubMed
description [Image: see text] Assembly by amyloid-beta (Aβ) peptides is vital for various neurodegenerative diseases. The process can be accelerated by hydrophobic interfaces such as the cell membrane interface and the air–water interface. Elucidating the assembly mechanism for Aβ peptides at hydrophobic interface requires knowledge of the microscopic structure of interfacial peptides. Here we combine scanning force microscopy, sum-frequency generation spectroscopy, and metadynamics simulations to probe the structure of the central fragment of Aβ peptides at the air–water interface. We find that the structure of interfacial peptides depends on pH: at neutral pH, the peptides adopt a less folded, bending motif by forming intra-hydrogen bonds; at acidic pH, the peptides refold into extended β-strand fibril conformation, which further promotes their macroscopic assembly. The conformational transition of interfacial peptides is driven by the reduced hydrogen bonds, both with water and within peptides, resulting from the protonation of acidic glutamic acid side chains.
format Online
Article
Text
id pubmed-9340808
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher American Chemical Society
record_format MEDLINE/PubMed
spelling pubmed-93408082022-08-02 Acidic pH Promotes Refolding and Macroscopic Assembly of Amyloid β (16–22) Peptides at the Air–Water Interface Lu, Hao Bellucci, Luca Sun, Shumei Qi, Daizong Rosa, Marta Berger, Rüdiger Corni, Stefano Bonn, Mischa J Phys Chem Lett [Image: see text] Assembly by amyloid-beta (Aβ) peptides is vital for various neurodegenerative diseases. The process can be accelerated by hydrophobic interfaces such as the cell membrane interface and the air–water interface. Elucidating the assembly mechanism for Aβ peptides at hydrophobic interface requires knowledge of the microscopic structure of interfacial peptides. Here we combine scanning force microscopy, sum-frequency generation spectroscopy, and metadynamics simulations to probe the structure of the central fragment of Aβ peptides at the air–water interface. We find that the structure of interfacial peptides depends on pH: at neutral pH, the peptides adopt a less folded, bending motif by forming intra-hydrogen bonds; at acidic pH, the peptides refold into extended β-strand fibril conformation, which further promotes their macroscopic assembly. The conformational transition of interfacial peptides is driven by the reduced hydrogen bonds, both with water and within peptides, resulting from the protonation of acidic glutamic acid side chains. American Chemical Society 2022-07-15 2022-07-28 /pmc/articles/PMC9340808/ /pubmed/35839425 http://dx.doi.org/10.1021/acs.jpclett.2c01171 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Lu, Hao
Bellucci, Luca
Sun, Shumei
Qi, Daizong
Rosa, Marta
Berger, Rüdiger
Corni, Stefano
Bonn, Mischa
Acidic pH Promotes Refolding and Macroscopic Assembly of Amyloid β (16–22) Peptides at the Air–Water Interface
title Acidic pH Promotes Refolding and Macroscopic Assembly of Amyloid β (16–22) Peptides at the Air–Water Interface
title_full Acidic pH Promotes Refolding and Macroscopic Assembly of Amyloid β (16–22) Peptides at the Air–Water Interface
title_fullStr Acidic pH Promotes Refolding and Macroscopic Assembly of Amyloid β (16–22) Peptides at the Air–Water Interface
title_full_unstemmed Acidic pH Promotes Refolding and Macroscopic Assembly of Amyloid β (16–22) Peptides at the Air–Water Interface
title_short Acidic pH Promotes Refolding and Macroscopic Assembly of Amyloid β (16–22) Peptides at the Air–Water Interface
title_sort acidic ph promotes refolding and macroscopic assembly of amyloid β (16–22) peptides at the air–water interface
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9340808/
https://www.ncbi.nlm.nih.gov/pubmed/35839425
http://dx.doi.org/10.1021/acs.jpclett.2c01171
work_keys_str_mv AT luhao acidicphpromotesrefoldingandmacroscopicassemblyofamyloidb1622peptidesattheairwaterinterface
AT bellucciluca acidicphpromotesrefoldingandmacroscopicassemblyofamyloidb1622peptidesattheairwaterinterface
AT sunshumei acidicphpromotesrefoldingandmacroscopicassemblyofamyloidb1622peptidesattheairwaterinterface
AT qidaizong acidicphpromotesrefoldingandmacroscopicassemblyofamyloidb1622peptidesattheairwaterinterface
AT rosamarta acidicphpromotesrefoldingandmacroscopicassemblyofamyloidb1622peptidesattheairwaterinterface
AT bergerrudiger acidicphpromotesrefoldingandmacroscopicassemblyofamyloidb1622peptidesattheairwaterinterface
AT cornistefano acidicphpromotesrefoldingandmacroscopicassemblyofamyloidb1622peptidesattheairwaterinterface
AT bonnmischa acidicphpromotesrefoldingandmacroscopicassemblyofamyloidb1622peptidesattheairwaterinterface