Aggregation of Chameleon Peptides: Implications of α-Helicity in Fibril Formation
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- 作者：Bongkeun Kim ; Thanh D. Do ; Eric Y. Hayden ; David B. Teplow ; Michael T. Bowers ; Joan-Emma Shea
- 刊名：Journal of Physical Chemistry B
- 出版年：2016
- 出版时间：July 7, 2016
- 年：2016
- 卷：120
- 期：26
- 页码：5874-5883
- 全文大小：653K
- 年卷期：0
- ISSN：1520-5207
文摘
We investigate the relationship between the inherent secondary structure and aggregation propensity of peptides containing chameleon sequences (i.e., sequences that can adopt either α or β structure depending on context) using a combination of replica exchange molecular dynamics simulations, ion-mobility mass spectrometry, circular dichroism, and transmission electron microscopy. We focus on an eight-residue long chameleon sequence that can adopt an α-helical structure in the context of the iron-binding protein from Bacillus anthracis (PDB id 1JIG) and a β-strand in the context of the baculovirus P35 protein (PDB id 1P35). We show that the isolated chameleon sequence is intrinsically disordered, interconverting between α-helical and β-rich conformations. The inherent conformational plasticity of the sequence can be constrained by addition of flanking residues with a given secondary structure propensity. Intriguingly, we show that the chameleon sequence with helical flanking residues aggregates rapidly into fibrils, whereas the chameleon sequence with flanking residues that favor β-conformations has weak aggregation propensity. This work sheds new insights into the possible role of α-helical intermediates in fibril formation.