Essential Role of Histidine for Rapid Copper(II)-Mediated Disassembly of Neurokinin B Amyloid
Neurokinin B is a tachykinin peptide involved in a diverse range of neuronal functions. It rapidly forms an amyloid, which is considered physiologically important for efficient packing into dense core secretory vesicles within hypothalamic neurons. Disassembly of the amyloid is thought to require th...
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MDPI AG
2022-10-01
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author | Bhawantha M. Jayawardena Lorraine Peacey Roland Gamsjaeger Christopher E. Jones |
author_facet | Bhawantha M. Jayawardena Lorraine Peacey Roland Gamsjaeger Christopher E. Jones |
author_sort | Bhawantha M. Jayawardena |
collection | DOAJ |
description | Neurokinin B is a tachykinin peptide involved in a diverse range of neuronal functions. It rapidly forms an amyloid, which is considered physiologically important for efficient packing into dense core secretory vesicles within hypothalamic neurons. Disassembly of the amyloid is thought to require the presence of copper ions, which interact with histidine at the third position in the peptide sequence. However, it is unclear how the histidine is involved in the amyloid structure and why copper coordination can trigger disassembly. In this work, we demonstrate that histidine contributes to the amyloid structure via π-stacking interactions with nearby phenylalanine residues. The ability of neurokinin B to form an amyloid is dependent on any aromatic residue at the third position in the sequence; however, only the presence of histidine leads to both amyloid formation and rapid copper-induced disassembly. |
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issn | 2218-273X |
language | English |
last_indexed | 2024-03-09T19:14:09Z |
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spelling | doaj.art-64f972f422d64fdf8c105be5e8dcaf372023-11-24T03:53:01ZengMDPI AGBiomolecules2218-273X2022-10-011211158510.3390/biom12111585Essential Role of Histidine for Rapid Copper(II)-Mediated Disassembly of Neurokinin B AmyloidBhawantha M. Jayawardena0Lorraine Peacey1Roland Gamsjaeger2Christopher E. Jones3School of Science, Western Sydney University, Locked Bag 1797, Penrith 2751, AustraliaSchool of Science, Western Sydney University, Locked Bag 1797, Penrith 2751, AustraliaSchool of Science, Western Sydney University, Locked Bag 1797, Penrith 2751, AustraliaSchool of Science, Western Sydney University, Locked Bag 1797, Penrith 2751, AustraliaNeurokinin B is a tachykinin peptide involved in a diverse range of neuronal functions. It rapidly forms an amyloid, which is considered physiologically important for efficient packing into dense core secretory vesicles within hypothalamic neurons. Disassembly of the amyloid is thought to require the presence of copper ions, which interact with histidine at the third position in the peptide sequence. However, it is unclear how the histidine is involved in the amyloid structure and why copper coordination can trigger disassembly. In this work, we demonstrate that histidine contributes to the amyloid structure via π-stacking interactions with nearby phenylalanine residues. The ability of neurokinin B to form an amyloid is dependent on any aromatic residue at the third position in the sequence; however, only the presence of histidine leads to both amyloid formation and rapid copper-induced disassembly.https://www.mdpi.com/2218-273X/12/11/1585copperneurokinintachykininamyloid |
spellingShingle | Bhawantha M. Jayawardena Lorraine Peacey Roland Gamsjaeger Christopher E. Jones Essential Role of Histidine for Rapid Copper(II)-Mediated Disassembly of Neurokinin B Amyloid Biomolecules copper neurokinin tachykinin amyloid |
title | Essential Role of Histidine for Rapid Copper(II)-Mediated Disassembly of Neurokinin B Amyloid |
title_full | Essential Role of Histidine for Rapid Copper(II)-Mediated Disassembly of Neurokinin B Amyloid |
title_fullStr | Essential Role of Histidine for Rapid Copper(II)-Mediated Disassembly of Neurokinin B Amyloid |
title_full_unstemmed | Essential Role of Histidine for Rapid Copper(II)-Mediated Disassembly of Neurokinin B Amyloid |
title_short | Essential Role of Histidine for Rapid Copper(II)-Mediated Disassembly of Neurokinin B Amyloid |
title_sort | essential role of histidine for rapid copper ii mediated disassembly of neurokinin b amyloid |
topic | copper neurokinin tachykinin amyloid |
url | https://www.mdpi.com/2218-273X/12/11/1585 |
work_keys_str_mv | AT bhawanthamjayawardena essentialroleofhistidineforrapidcopperiimediateddisassemblyofneurokininbamyloid AT lorrainepeacey essentialroleofhistidineforrapidcopperiimediateddisassemblyofneurokininbamyloid AT rolandgamsjaeger essentialroleofhistidineforrapidcopperiimediateddisassemblyofneurokininbamyloid AT christopherejones essentialroleofhistidineforrapidcopperiimediateddisassemblyofneurokininbamyloid |