School of Science, Western Sydney University, Locked Bag 1797, Penrith 2751, Australia.
Biomolecules. 2022 Oct 28;12(11):1585. doi: 10.3390/biom12111585.
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.
神经激肽 B 是一种速激肽肽，参与多种神经元功能。它迅速形成淀粉样蛋白，这被认为对于在下丘脑神经元中高效包装到致密核心分泌小泡中是生理上重要的。淀粉样蛋白的解体被认为需要铜离子的存在，铜离子与肽序列中第三位的组氨酸相互作用。然而，组氨酸如何参与淀粉样蛋白结构以及为什么铜配位可以触发解体尚不清楚。在这项工作中，我们证明组氨酸通过与附近苯丙氨酸残基的π-堆积相互作用有助于淀粉样蛋白结构。神经激肽 B 形成淀粉样蛋白的能力取决于序列中第三位的任何芳香族残基；然而，只有组氨酸的存在才会导致淀粉样蛋白的形成和快速的铜诱导解体。
