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Intramolecular H-Bonds Govern the Recognition of a Flexible Peptide by an Antibody

45 Pages Posted: 11 Apr 2018 Sneak Peek Status: Review Complete

See all articles by Kazuhiro Miyanabe

Kazuhiro Miyanabe

University of Tokyo - Department of Chemistry and Biotechnology

Hiroki Akiba

University of Tokyo - Department of Bioengineering

Daisuke Kuroda

University of Tokyo - Department of Bioengineering

Makoto Nakakido

University of Tokyo - Department of Bioengineering

Osamu Kusano-Arai

University of Tokyo - Department of Quantitative Biology and Medicine

Hiroko Iwanari

University of Tokyo - Department of Quantitative Biology and Medicine

Takao Hamakubo

University of Tokyo - Department of Quantitative Biology and Medicine

Jose M. M. Caaveiro

University of Tokyo - Department of Bioengineering

Kouhei Tsumoto

University of Tokyo - Department of Chemistry and Biotechnology

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Abstract

Molecular recognition is a fundamental event at the core of essentially every biological process. In particular, intermolecular H-bonds have been recognized as key stabilizing forces in antibody-antigen interactions resulting in exquisite specificity and high affinity. Although equally abundant, the role of intramolecular H-bonds is far less clear, and not universally acknowledged. Herein we have carried out a molecular-level study to dissect the contribution of intramolecular H-bonds in a flexible peptide for the recognition by an antibody. We show that intramolecular H-bonds may have a profound, multifaceted, and deleterious effect on the binding affinity by up to 2 kcal mol-1 of free energy. Collectively, our results suggest that antibodies are fine-tuned to recognize transiently stabilized structures of flexible peptides in solution, for which intramolecular H-bonds play a key role. Our results have implications for the design of more efficient vaccines employing short peptides.

Suggested Citation

Miyanabe, Kazuhiro and Akiba, Hiroki and Kuroda, Daisuke and Nakakido, Makoto and Kusano-Arai, Osamu and Iwanari, Hiroko and Hamakubo, Takao and Caaveiro, Jose M. M. and Tsumoto, Kouhei, Intramolecular H-Bonds Govern the Recognition of a Flexible Peptide by an Antibody (2018). Available at SSRN: https://ssrn.com/abstract=3155851 or http://dx.doi.org/10.2139/ssrn.3155851
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Kazuhiro Miyanabe

University of Tokyo - Department of Chemistry and Biotechnology

7-3-1 Hongo
Tokyo, Bunkyo-ku 113-8656
Japan

Hiroki Akiba

University of Tokyo - Department of Bioengineering

7-3-1 Hongo
1st Floor, 5th Building
Tokyo, Bunkyo-ku
Japan

Daisuke Kuroda

University of Tokyo - Department of Bioengineering

7-3-1 Hongo
1st Floor, 5th Building
Tokyo, Bunkyo-ku
Japan

Makoto Nakakido

University of Tokyo - Department of Bioengineering

7-3-1 Hongo
1st Floor, 5th Building
Tokyo, Bunkyo-ku
Japan

Osamu Kusano-Arai

University of Tokyo - Department of Quantitative Biology and Medicine

4-6-1 Komaba
Komaba II Campus, RCAST Building 4, Room 317
Tokyo, Meguro-ku 153-8904
Japan

Hiroko Iwanari

University of Tokyo - Department of Quantitative Biology and Medicine

4-6-1 Komaba
Komaba II Campus, RCAST Building 4, Room 317
Tokyo, Meguro-ku 153-8904
Japan

Takao Hamakubo

University of Tokyo - Department of Quantitative Biology and Medicine

4-6-1 Komaba
Komaba II Campus, RCAST Building 4, Room 317
Tokyo, Meguro-ku 153-8904
Japan

Jose M. M. Caaveiro

University of Tokyo - Department of Bioengineering ( email )

7-3-1 Hongo
1st Floor, 5th Building
Tokyo, Bunkyo-ku
Japan

Kouhei Tsumoto (Contact Author)

University of Tokyo - Department of Chemistry and Biotechnology ( email )

7-3-1 Hongo
Tokyo, Bunkyo-ku 113-8656
Japan

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