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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Main Authors: Bhawantha M. Jayawardena, Lorraine Peacey, Roland Gamsjaeger, Christopher E. Jones
Format: Article
Language:English
Published: MDPI AG 2022-10-01
Series:Biomolecules
Subjects:
Online Access:https://www.mdpi.com/2218-273X/12/11/1585
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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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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
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AT rolandgamsjaeger essentialroleofhistidineforrapidcopperiimediateddisassemblyofneurokininbamyloid
AT christopherejones essentialroleofhistidineforrapidcopperiimediateddisassemblyofneurokininbamyloid