| Autor: |
Kim, B, Do, TD, Hayden, EY, Teplow, DB, Bowers, MT, Shea, J-E |
| Jazyk: |
angličtina |
| Rok vydání: |
2016 |
| Zdroj: |
Kim, B; Do, TD; Hayden, EY; Teplow, DB; Bowers, MT; & Shea, J-E. (2016). Aggregation of Chameleon Peptides: Implications of alpha-Helicity in Fibril Formation. JOURNAL OF PHYSICAL CHEMISTRY B, 120(26), 5874-5883. doi: 10.1021/acs.jpcb.6b00830. UCLA: Retrieved from: http://www.escholarship.org/uc/item/46z0d0ht |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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