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Heat denaturation of the antibody, a multi-domain protein

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Abstract

The antibody is one of the most well-studied multi-domain proteins because of its abundance and physiological importance. In this article, we describe the effect of the complex, multi-domain structure of the antibody on its denaturation by heat. Natural antibodies are composed of 6 to 70 immunoglobulin fold domains, and are irreversibly denatured at high temperatures. Although the separated single immunoglobulin fold domain can be refolded after heat denaturation, denaturation of pairs of such domains is irreversible. Each antibody subclass exhibits a distinct heat tolerance, and IgE is especially known to be heat-labile. IgE starts unfolding at a lower temperature compared to other antibodies, because of the low stability of its CH3 domain. Each immunoglobulin domain starts unfolding at different temperatures. For instance, the CH3 domain of IgG unfolds at a higher temperature than its CH2 domain. Thus, the antibody has a mixture of folded and unfolded structures at a certain temperature. Co-existence of these folded and unfolded domains in a single polypeptide chain may increase the tendency to aggregate which causes the inactivation of the antibody.

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Authors and Affiliations

  1. Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 1-8-31 Midorigaoka, Ikeda, Osaka, 563-8577, Japan

    Yoko Akazawa-Ogawa, Hidenori Nagai & Yoshihisa Hagihara

  2. AIST-Osaka University Advanced Photonics and Biosensing Open Innovation Laboratory, National Institute of Advanced Industrial Science and Technology (AIST), 2-1 Yamada-Oka, Suita, Osaka, 565-0871, Japan

    Hidenori Nagai

Authors
  1. Yoko Akazawa-Ogawa
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  2. Hidenori Nagai
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  3. Yoshihisa Hagihara
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Correspondence to Yoshihisa Hagihara.

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Yoko Akazawa-Ogawa declares that she has no conflict of interest. Hidenori Nagai declares that he has no conflict of interest. Yoshihisa Hagihara declares that he has no conflict of interest.

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Additional information

This article is part of a Special Issue on ‘Biomolecules to Bio-nanomachines - Fumio Arisaka 70th Birthday’ edited by Damien Hall, Junichi Takagi and Haruki Nakamura.

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Akazawa-Ogawa, Y., Nagai, H. & Hagihara, Y. Heat denaturation of the antibody, a multi-domain protein. Biophys Rev 10, 255–258 (2018). https://doi.org/10.1007/s12551-017-0361-8

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  • DOI: https://doi.org/10.1007/s12551-017-0361-8

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