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An Unusual Protein–Protein Interaction through Coupled Unfolding and Binding
Author(s) -
Yu TaeKyung,
Shin SeungA,
Kim EunHee,
Kim Sunghyun,
Ryu KyungSeok,
Cheong Haekap,
Ahn HeeChul,
Jon Sangyong,
Suh JeongYong
Publication year - 2014
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201404750
Subject(s) - chemistry , intramolecular force , biophysics , intermolecular force , plasma protein binding , crystallography , binding site , scaffold protein , fibronectin , scaffold , stereochemistry , biochemistry , molecule , biology , organic chemistry , extracellular matrix , medicine , signal transduction , biomedical engineering
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.