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An Insight into the Thermodynamic Characteristics of Human Thrombopoietin Complexation with TN1 Antibody
https://repo.qst.go.jp/records/47562
https://repo.qst.go.jp/records/47562cc5fb9b1-da8b-4df6-a200-009c32eea0c6
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2016-10-06 | |||||
| タイトル | ||||||
| タイトル | An Insight into the Thermodynamic Characteristics of Human Thrombopoietin Complexation with TN1 Antibody | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Arai, Shigeki
× Arai, Shigeki× Shibazaki, Chie× Adachi, Motoyasu× Honjo, Eijiro× Tamada, Taro× Maeda, Yoshitake× Tahara, Tomoyuki× Kato, Takashi× Miyazaki, Hiroshi× Blaber, Michael× Kuroki, Ryota× 新井 栄揮× 柴崎 千枝× 安達 基泰× 玉田 太郎× 加藤 尚志 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Human thrombopoietin (hTPO) primarily stimulates megakaryocytopoiesis and platelet production and is neutralized by the mouse TN1 antibody. The thermodynamic characteristics of TN1 antibody–hTPO complexation were analyzed by isothermal titration calorimetry (ITC) using an antigen-binding fragment (Fab) derived from the TN1 antibody (TN1-Fab). To clarify the mechanism by which hTPO is recognized by TN1-Fab the conformation of free TN1-Fab was determined to a resolution of 2.0 Å using X-ray crystallography and compared with the hTPO-bound form of TN1-Fab determined by a previous study. This structural comparison revealed that the conformation of TN1-Fab does not substantially change after hTPO binding and a set of 15 water molecules is released from the antigen-binding site (paratope) of TN1-Fab upon hTPO complexation. Interestingly, the heat capacity change (ΔCp) measured by ITC (-1.52 ± 0.05 kJ mol-1 K-1) differed significantly from calculations based upon the X-ray structure data of the hTPO-bound and unbound forms of TN1-Fab (0.25 – -1.02 kJ mol-1 K-1) suggesting that hTPO undergoes an induced-fit conformational change combined with significant desolvation upon TN1-Fab binding. The results shed light on the structural biology associated with neutralizing antibody recognition. | |||||
| 書誌情報 |
Protein Science 巻 25, 号 10, p. 1786-1796, 発行日 2016-08 |
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| 出版者 | ||||||
| 出版者 | The Protein Society | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1002/pro.2985 | |||||
