Biophysical Reviews

, Volume 10, Issue 2, pp 255–258 | Cite as

Heat denaturation of the antibody, a multi-domain protein

  • Yoko Akazawa-Ogawa
  • Hidenori Nagai
  • Yoshihisa Hagihara
Review

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.

Keywords

Antibody Heat denaturation Aggregation Protein stability Single-domain antibody 

Notes

Compliance with ethical standards

Conflict of interest

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.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

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Copyright information

© International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Biomedical Research InstituteNational Institute of Advanced Industrial Science and Technology (AIST)IkedaJapan
  2. 2.AIST-Osaka University Advanced Photonics and Biosensing Open Innovation LaboratoryNational Institute of Advanced Industrial Science and Technology (AIST)SuitaJapan

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