Preparation of alpaca-derived nanobody which activatites ghrelin receptor and its application to the crystal structure analysis
| Project/Area Number |
16K07281
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Structural biochemistry
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| Research Institution | Kurume University |
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Principal Investigator |
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| Research Collaborator |
Sawazaki Tatsuya
Takeda Hiroyuki
Ito Yuji
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | ペプチドホルモン / グレリン / グレリン受容体 / GPCR / 結晶構造解析 / 膜タンパク質 / ナノボディ / アルパカ / 結晶構造 / ペプチドホルモン受容体 / 立体構造認識 / GPCR結晶化 / パンニング |
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| Outline of Final Research Achievements |
Alpaca nanobodies that specifically recognize the conformation of the ghrelin receptor have not been obtained yet. It is necessary to continue the screening further in the future. On the other hand, it was possible to obtain a mouse monoclonal antibody against the ghrelin receptor, and using this antibody for a crystallization, it was possible to obtain a structure of the inactive ghrelin receptor. It was assumed that the phenylalanine cluster between TM6 and TM7 interacts with the fatty acid modifying group of ghrelin, thereby changing the ghrelin receptor to the active form. This clarified one of the reasons why octanoate of ghrelin is required for receptor activity.
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| Academic Significance and Societal Importance of the Research Achievements |
グレリンは典型的なGタンパク質共役型受容体(GPCR)であるグレリン受容体に結合して、その生理作用を現す。グレリンはペプチド・ホルモンであるが、N末端から3番目のセリン残基が中鎖脂肪酸のオクタン酸によって修飾されており、しかもこのオクタン酸が受容体の活性化に必須であるという極めて珍しい構造をしている。今回の研究によって、なぜグレリンがペプチド部分だけでは受容体を活性化できず、オクタン酸の修飾があって始めて受容体を活性化できるのかが明らかになった。この知見はグレリン受容体の新しいアゴニストやアンタゴニストの合成に応用でき、摂食障害や食欲不振症などへの応用が期待される。
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Report
(4 results)
Research Products
(13 results)
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[Journal Article] Helicobacter pylori Vacuolating Cytotoxin A Causes Anorexia and Anxiety via Hypothalamic Urocortin 1 in Mice2019
Author(s)
Suzuki H, Ataka K, Asakawa A, Cheng KC, Ushikai M, Iwai H, Yagi T, Arai T, Yahiro K, Yamamoto K, Yokoyama Y, Kojima M, Yada T, Hirayama T, Nakamura N, Inui A
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Journal Title
Sci Rep
Volume: 9
Issue: 1
Pages: 6011-6011
DOI
Related Report
Peer Reviewed / Open Access
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