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Orientation of tyrosine side chain in neurotoxic Aβ differs in two different secondary structures of the peptide
Amyloid β (Aβ) peptide is present as a major component in amyloid plaque that is one of the hallmarks of Alzheimer's disease. The peptide contains a single tyrosine residue and Aβ has a major implication in the pathology of the disease progression. Current investigation revealed that the tyrosi...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5098961/ https://www.ncbi.nlm.nih.gov/pubmed/27853536 http://dx.doi.org/10.1098/rsos.160112 |
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author | Das, Swagata Das, Supriya Roy, Anupam Pal, Uttam Maiti, Nakul C. |
author_facet | Das, Swagata Das, Supriya Roy, Anupam Pal, Uttam Maiti, Nakul C. |
author_sort | Das, Swagata |
collection | PubMed |
description | Amyloid β (Aβ) peptide is present as a major component in amyloid plaque that is one of the hallmarks of Alzheimer's disease. The peptide contains a single tyrosine residue and Aβ has a major implication in the pathology of the disease progression. Current investigation revealed that the tyrosine side chain attained two different critical stereo orientations in two dissimilar conformational states of the peptide. The extended α-helical structure of the peptide observed in an apolar solvent or methanol/water mixture became disordered in aqueous medium and the radius of gyration decreased. In aqueous medium, the torsional angle around C(α)–C(β) of tyrosine group became −60°. However, in its α-helical conformation in an apolar system, the measured angle was 180° and this rotameric state may be reasoned behind stronger tyrosine fluorescence compared with the disordered state of the peptide. Molecular dynamics simulation analyses and spectroscopic studies have helped us to understand the major structural changes in the secondary structure of the peptide in the two conformational states. A conformational clustering indicated that the compact state is more stable with tyrosine residue attaining the torsion angle value of −60°, whereas the native state (in HFIP/water mixture) is prevalent at a torsion angle value of −180°. High solvent accessibility has possibly stabilized the particular rotameric state (−60°) of the tyrosine residue and could be the reason behind decrease in fluorescence of the sole tyrosine residue in an aqueous buffer solution (pH 7.4) compared with its fluorescence in the α-helical structure in the micellar environment. |
format | Online Article Text |
id | pubmed-5098961 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The Royal Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-50989612016-11-16 Orientation of tyrosine side chain in neurotoxic Aβ differs in two different secondary structures of the peptide Das, Swagata Das, Supriya Roy, Anupam Pal, Uttam Maiti, Nakul C. R Soc Open Sci Biochemistry and Biophysics Amyloid β (Aβ) peptide is present as a major component in amyloid plaque that is one of the hallmarks of Alzheimer's disease. The peptide contains a single tyrosine residue and Aβ has a major implication in the pathology of the disease progression. Current investigation revealed that the tyrosine side chain attained two different critical stereo orientations in two dissimilar conformational states of the peptide. The extended α-helical structure of the peptide observed in an apolar solvent or methanol/water mixture became disordered in aqueous medium and the radius of gyration decreased. In aqueous medium, the torsional angle around C(α)–C(β) of tyrosine group became −60°. However, in its α-helical conformation in an apolar system, the measured angle was 180° and this rotameric state may be reasoned behind stronger tyrosine fluorescence compared with the disordered state of the peptide. Molecular dynamics simulation analyses and spectroscopic studies have helped us to understand the major structural changes in the secondary structure of the peptide in the two conformational states. A conformational clustering indicated that the compact state is more stable with tyrosine residue attaining the torsion angle value of −60°, whereas the native state (in HFIP/water mixture) is prevalent at a torsion angle value of −180°. High solvent accessibility has possibly stabilized the particular rotameric state (−60°) of the tyrosine residue and could be the reason behind decrease in fluorescence of the sole tyrosine residue in an aqueous buffer solution (pH 7.4) compared with its fluorescence in the α-helical structure in the micellar environment. The Royal Society 2016-10-05 /pmc/articles/PMC5098961/ /pubmed/27853536 http://dx.doi.org/10.1098/rsos.160112 Text en © 2016 The Authors. http://creativecommons.org/licenses/by/4.0/ Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited. |
spellingShingle | Biochemistry and Biophysics Das, Swagata Das, Supriya Roy, Anupam Pal, Uttam Maiti, Nakul C. Orientation of tyrosine side chain in neurotoxic Aβ differs in two different secondary structures of the peptide |
title | Orientation of tyrosine side chain in neurotoxic Aβ differs in two different secondary structures of the peptide |
title_full | Orientation of tyrosine side chain in neurotoxic Aβ differs in two different secondary structures of the peptide |
title_fullStr | Orientation of tyrosine side chain in neurotoxic Aβ differs in two different secondary structures of the peptide |
title_full_unstemmed | Orientation of tyrosine side chain in neurotoxic Aβ differs in two different secondary structures of the peptide |
title_short | Orientation of tyrosine side chain in neurotoxic Aβ differs in two different secondary structures of the peptide |
title_sort | orientation of tyrosine side chain in neurotoxic aβ differs in two different secondary structures of the peptide |
topic | Biochemistry and Biophysics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5098961/ https://www.ncbi.nlm.nih.gov/pubmed/27853536 http://dx.doi.org/10.1098/rsos.160112 |
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