Tyrosine Sulfation Restricts the Conformational Ensemble of a Flexible Peptide, Strengthening the Binding Affinity for an Antibody

Kazuhiro Miyanabe, Takefumi Yamashita, Yoshito Abe, Hiroki Akiba, Yuichiro Takamatsu, Makoto Nakakido, Takao Hamakubo, Tadashi Ueda, Jose M.M. Caaveiro, Kouhei Tsumoto

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Protein tyrosine sulfation (PTS) is a post-translational modification regulating numerous biological events. PTS generally occurs at flexible regions of proteins, enhancing intermolecular interactions between proteins. Because of the high flexibility associated with the regions where PTS is generally encountered, an atomic-level understanding has been difficult to achieve by X-ray crystallography or nuclear magnetic resonance techniques. In this study, we focused on the conformational behavior of a flexible sulfated peptide and its interaction with an antibody. Molecular dynamics simulations and thermodynamic analysis indicated that PTS reduced the main-chain fluctuations upon the appearance of sulfate-mediated intramolecular H-bonds. Collectively, our data suggested that one of the mechanisms by which PTS may enhance protein-protein interactions consists of the limitation of conformational dynamics in the unbound state, thus reducing the loss of entropy upon binding and boosting the affinity for its partner.

Original languageEnglish
Pages (from-to)4177-4185
Number of pages9
JournalBiochemistry
Volume57
Issue number28
DOIs
Publication statusPublished - Jul 17 2018

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this