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...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
The Royal Society
2016-01-01
|
| Series: | Royal Society Open Science |
| Subjects: | |
| Online Access: | https://royalsocietypublishing.org/doi/pdf/10.1098/rsos.160112 |
| _version_ | 1818259746851913728 |
|---|---|
| author | Swagata Das Supriya Das Anupam Roy Uttam Pal Nakul C. Maiti |
| author_facet | Swagata Das Supriya Das Anupam Roy Uttam Pal Nakul C. Maiti |
| author_sort | Swagata Das |
| collection | DOAJ |
| 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 Cα–Cβ 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. |
| first_indexed | 2024-12-12T18:20:21Z |
| format | Article |
| id | doaj.art-214db69beffa4c388efdbbecf2fc7e64 |
| institution | Directory Open Access Journal |
| issn | 2054-5703 |
| language | English |
| last_indexed | 2024-12-12T18:20:21Z |
| publishDate | 2016-01-01 |
| publisher | The Royal Society |
| record_format | Article |
| series | Royal Society Open Science |
| spelling | doaj.art-214db69beffa4c388efdbbecf2fc7e642022-12-22T00:16:10ZengThe Royal SocietyRoyal Society Open Science2054-57032016-01-0131010.1098/rsos.160112160112Orientation of tyrosine side chain in neurotoxic Aβ differs in two different secondary structures of the peptideSwagata DasSupriya DasAnupam RoyUttam PalNakul C. MaitiAmyloid 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 Cα–Cβ 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.https://royalsocietypublishing.org/doi/pdf/10.1098/rsos.160112aβ peptidetyrosine fluorescenceconformationrotamer |
| spellingShingle | Swagata Das Supriya Das Anupam Roy Uttam Pal Nakul C. Maiti Orientation of tyrosine side chain in neurotoxic Aβ differs in two different secondary structures of the peptide Royal Society Open Science aβ peptide tyrosine fluorescence conformation rotamer |
| 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 | aβ peptide tyrosine fluorescence conformation rotamer |
| url | https://royalsocietypublishing.org/doi/pdf/10.1098/rsos.160112 |
| work_keys_str_mv | AT swagatadas orientationoftyrosinesidechaininneurotoxicabdiffersintwodifferentsecondarystructuresofthepeptide AT supriyadas orientationoftyrosinesidechaininneurotoxicabdiffersintwodifferentsecondarystructuresofthepeptide AT anupamroy orientationoftyrosinesidechaininneurotoxicabdiffersintwodifferentsecondarystructuresofthepeptide AT uttampal orientationoftyrosinesidechaininneurotoxicabdiffersintwodifferentsecondarystructuresofthepeptide AT nakulcmaiti orientationoftyrosinesidechaininneurotoxicabdiffersintwodifferentsecondarystructuresofthepeptide |