Copper ions trigger disassembly of neurokinin B functional amyloid and inhibit de novo assembly.

Abstract:

:The formation of amyloid is considered an intrinsic ability of most polypeptides. It is a structure adopted by many neuropeptides and neurohormones during the formation of dense core vesicles in secretory cells, yet the mechanisms mediating assembly and disassembly of these amyloids remain unclear. Neurokinin B is a neuropeptide thought to form an amyloid in secretory cells. It is known to coordinate copper, but the physiological significance of metal binding is not known. In this work we explored the amyloid formation of neurokinin B and the impact that metals had on the aggregation behaviour. We show that the production of neurokinin B amyloid is dependent on the phosphate concentration, the pH and the presence of a histidine at position 3 in the primary sequence. Copper(II) and nickel(II) coordination to the peptide, which requires the histidine imidazole group, completely inhibits amyloid formation, whereas zinc(II) slows, but does not inhibit fibrillogenesis. Furthermore, we show that copper(II) can rapidly disassemble preformed neurokinin B amyloid. This work identifies a role for copper in neurokinin B structure and reveals a mechanism for amyloid assembly and disassembly dependent on metal coordination.

journal_name

J Struct Biol

authors

Jayawardena BM,Jones MR,Hong Y,Jones CE

doi

10.1016/j.jsb.2019.09.011

subject

Has Abstract

pub_date

2019-12-01 00:00:00

pages

107394

issue

3

eissn

1047-8477

issn

1095-8657

pii

S1047-8477(19)30205-9

journal_volume

208

pub_type

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