Monoclonal antibody that activates the ghrelin receptor and its application to the crystal structure analysis

2016 Fiscal Year Final Research Report

• Project/Area Number: 26650025
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Structural biochemistry
• Research Institution: Kurume University
• Principal Investigator: Kojima Masayasu 久留米大学, 分子生命科学研究所, 教授 (20202062)
• Research Collaborator: Shiimura Yuki
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: グレリン / オクタン酸 / グレリン受容体 / GPCR / 脂肪酸修飾 / モノクローナル抗体 / ナノボディ / 立体構造認識抗体

Outline of Final Research Achievements

In order to clarify how this fatty acid modified ghrelin binds to and activates the ghrelin receptor, we started on elucidating the crystal structure of the ghrelin receptor. However, the ghrelin receptor is a typical GPCR, and it is generally difficult to analyze the crystal structure of GPCR. Furthermore, it is more difficult to analyze the crystal structure of an active form receptor with an agonist bound thereto.
In this study, we tried to prepare monoclonal antibodies that act on the ghrelin receptor and can activate it. We planned to elucidate the crystal structure of the active ghrelin receptor by applying the monoclonal antibody to enlarge the hydrophilic surface of the ghrelin receptor and increasing its thermal stability.
As a result, we have obtained antibodies recognizing the steric structure of the ghrelin receptor, and are now applied the antibodies to the crystallization of the ghrelin receptor.

Free Research Field

構造生物学