title: An unusual protein-protein interaction through coupled unfolding and binding.
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.
authors.affiliation: Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-921 (South Korea).
authors.forename: Tae-Kyung
authors.initials: TK
authors.lastname: Yu
authors.forename: Seung-A
authors.initials: SA
authors.lastname: Shin
authors.forename: Eun-Hee
authors.initials: EH
authors.lastname: Kim
authors.forename: Sunghyun
authors.initials: S
authors.lastname: Kim
authors.forename: Kyung-Seok
authors.initials: KS
authors.lastname: Ryu
authors.forename: Haekap
authors.initials: H
authors.lastname: Cheong
authors.forename: Hee-Chul
authors.initials: HC
authors.lastname: Ahn
authors.forename: Sangyong
authors.initials: S
authors.lastname: Jon
authors.forename: Jeong-Yong
authors.initials: JY
authors.lastname: Suh
mesh_terms: D005353:Fibronectins / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D058767:Protein Unfolding
chemical_list: D005353:Fibronectins
keywords: NMR spectroscopy; aptides; fibronectin; protein folding; protein-protein interactions