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Structure of an antagonist-bound ghrelin receptor reveals possible ghrelin recognition mode

Ghrelin is a gastric peptide hormone with important physiological functions. The unique feature of ghrelin is its Serine 3 acyl-modification, which is essential for ghrelin’s activity. However, it remains to be elucidated why the acyl-modification of ghrelin is necessary for activity. To address the...

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Autores principales: Shiimura, Yuki, Horita, Shoichiro, Hamamoto, Akie, Asada, Hidetsugu, Hirata, Kunio, Tanaka, Misuzu, Mori, Kenji, Uemura, Tomoko, Kobayashi, Takuya, Iwata, So, Kojima, Masayasu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438500/
https://www.ncbi.nlm.nih.gov/pubmed/32814772
http://dx.doi.org/10.1038/s41467-020-17554-1
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author Shiimura, Yuki
Horita, Shoichiro
Hamamoto, Akie
Asada, Hidetsugu
Hirata, Kunio
Tanaka, Misuzu
Mori, Kenji
Uemura, Tomoko
Kobayashi, Takuya
Iwata, So
Kojima, Masayasu
author_facet Shiimura, Yuki
Horita, Shoichiro
Hamamoto, Akie
Asada, Hidetsugu
Hirata, Kunio
Tanaka, Misuzu
Mori, Kenji
Uemura, Tomoko
Kobayashi, Takuya
Iwata, So
Kojima, Masayasu
author_sort Shiimura, Yuki
collection PubMed
description Ghrelin is a gastric peptide hormone with important physiological functions. The unique feature of ghrelin is its Serine 3 acyl-modification, which is essential for ghrelin’s activity. However, it remains to be elucidated why the acyl-modification of ghrelin is necessary for activity. To address these questions, we solved the crystal structure of the ghrelin receptor bound to antagonist. The ligand-binding pocket of the ghrelin receptor is bifurcated by a salt bridge between E124 and R283. A striking feature of the ligand-binding pocket of the ghrelin receptor is a wide gap (crevasse) between the TM6 and TM7 bundles that is rich in hydrophobic amino acids, including a cluster of phenylalanine residues. Mutagenesis analyses suggest that the interaction between the gap structure and the acyl acid moiety of ghrelin may participate in transforming the ghrelin receptor into an active conformation.
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spelling pubmed-74385002020-08-28 Structure of an antagonist-bound ghrelin receptor reveals possible ghrelin recognition mode Shiimura, Yuki Horita, Shoichiro Hamamoto, Akie Asada, Hidetsugu Hirata, Kunio Tanaka, Misuzu Mori, Kenji Uemura, Tomoko Kobayashi, Takuya Iwata, So Kojima, Masayasu Nat Commun Article Ghrelin is a gastric peptide hormone with important physiological functions. The unique feature of ghrelin is its Serine 3 acyl-modification, which is essential for ghrelin’s activity. However, it remains to be elucidated why the acyl-modification of ghrelin is necessary for activity. To address these questions, we solved the crystal structure of the ghrelin receptor bound to antagonist. The ligand-binding pocket of the ghrelin receptor is bifurcated by a salt bridge between E124 and R283. A striking feature of the ligand-binding pocket of the ghrelin receptor is a wide gap (crevasse) between the TM6 and TM7 bundles that is rich in hydrophobic amino acids, including a cluster of phenylalanine residues. Mutagenesis analyses suggest that the interaction between the gap structure and the acyl acid moiety of ghrelin may participate in transforming the ghrelin receptor into an active conformation. Nature Publishing Group UK 2020-08-19 /pmc/articles/PMC7438500/ /pubmed/32814772 http://dx.doi.org/10.1038/s41467-020-17554-1 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Shiimura, Yuki
Horita, Shoichiro
Hamamoto, Akie
Asada, Hidetsugu
Hirata, Kunio
Tanaka, Misuzu
Mori, Kenji
Uemura, Tomoko
Kobayashi, Takuya
Iwata, So
Kojima, Masayasu
Structure of an antagonist-bound ghrelin receptor reveals possible ghrelin recognition mode
title Structure of an antagonist-bound ghrelin receptor reveals possible ghrelin recognition mode
title_full Structure of an antagonist-bound ghrelin receptor reveals possible ghrelin recognition mode
title_fullStr Structure of an antagonist-bound ghrelin receptor reveals possible ghrelin recognition mode
title_full_unstemmed Structure of an antagonist-bound ghrelin receptor reveals possible ghrelin recognition mode
title_short Structure of an antagonist-bound ghrelin receptor reveals possible ghrelin recognition mode
title_sort structure of an antagonist-bound ghrelin receptor reveals possible ghrelin recognition mode
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438500/
https://www.ncbi.nlm.nih.gov/pubmed/32814772
http://dx.doi.org/10.1038/s41467-020-17554-1
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