Abstract
Aptides, a novel class of high-affinity peptides, recognize diverse molecular targets with high affinity and specificity. The solution structure of the aptide APT specifically bound to fibronectin extradomain B (EDB), which represents an unusual protein-protein interaction that involves coupled unfolding and binding, is reported. APT binding is accompanied by unfolding of the C-terminal β strand of EDB, thereby permitting APT to interact with the freshly exposed hydrophobic interior surfaces of EDB. The β-hairpin scaffold of APT drives the interaction by a β-strand displacement mechanism, such that an intramolecular β sheet is replaced by an intermolecular β sheet. The unfolding of EDB perturbs the tight domain association between EDB and FN8 of fibronectin, thus highlighting its potential use as a scaffold that switches between stretched and bent conformations.
Original language | English |
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Pages (from-to) | 9784-9787 |
Number of pages | 4 |
Journal | Angewandte Chemie - International Edition |
Volume | 53 |
Issue number | 37 |
DOIs | |
State | Published - 8 Sep 2014 |
Keywords
- NMR spectroscopy
- aptides
- fibronectin
- protein folding
- protein-protein interactions