Intramolecular H-bonds govern the recognition of a flexible peptide by an antibody

• Published in: Journal of biochemistry (Tokyo) Vol. 164; no. 1; pp. 65 - 76
• Main Authors: Miyanabe, Kazuhiro, Akiba, Hiroki, Kuroda, Daisuke, Nakakido, Makoto, Kusano-Arai, Osamu, Iwanari, Hiroko, Hamakubo, Takao, Caaveiro, Jose M M, Tsumoto, Kouhei
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.07.2018
• Subjects: Antibodies - chemistry; Antigen-Antibody Reactions; Calorimetry; Hydrogen Bonding; Models, Molecular; Peptides - chemistry; Peptides - isolation & purification; Protein Refolding; molecular dynamics simulations; molecular recognition; antibody–antigen interaction; transient folding; unstructured peptide
• ISSN: 0021-924X; 1756-2651
• DOI: 10.1093/jb/mvy032

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 favorable 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.