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An Unusual Protein–Protein Interaction through Coupled Unfolding and Binding

Authors

  • Tae-Kyung Yu,

    1. Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-921 (South Korea)
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  • Seung-A Shin,

    1. Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-921 (South Korea)
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  • Eun-Hee Kim,

    1. Division of Magnetic Resonance, Korea Basic Science Institute, 16 Yeongudanji-Ro, Ochang, Chungbuk 363-883 (South Korea)
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  • Dr. Sunghyun Kim,

    1. KAIST Institute for the BioCentury, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Daejeon 305-701 (South Korea)
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  • Dr. Kyung-Seok Ryu,

    1. Division of Magnetic Resonance, Korea Basic Science Institute, 16 Yeongudanji-Ro, Ochang, Chungbuk 363-883 (South Korea)
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  • Dr. Haekap Cheong,

    1. Division of Magnetic Resonance, Korea Basic Science Institute, 16 Yeongudanji-Ro, Ochang, Chungbuk 363-883 (South Korea)
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  • Prof. Dr. Hee-Chul Ahn,

    1. Department of Pharmacy, Dongguk University-Seoul, Dongguk-ro 32, Ilsandong-gu, Goyang, Gyeonggi, 410-820 (South Korea)
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  • Prof. Dr. Sangyong Jon,

    1. KAIST Institute for the BioCentury, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Daejeon 305-701 (South Korea)
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  • Prof. Dr. Jeong-Yong Suh

    Corresponding author
    1. Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-921 (South Korea)
    • Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-921 (South Korea)

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  • This work was supported by a National Research Foundation of Korea (NRF) grant (2013R1A1A2010856). We thank the high-field NMR facility at the Korea Basic Science Institute and the National Center for Inter-University Research Facilities.

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.

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