Determination of the endothelin-1 recognition sites of endothelin receptor type A by the directed-degeneration method

Seong Gu Han; Sanghwan Ko; Won Kyu Lee; Sang Taek Jung; Yeon Gyu Yu

doi:10.1038/s41598-017-08096-6

Determination of the endothelin-1 recognition sites of endothelin receptor type A by the directed-degeneration method

Seong Gu Han, Sanghwan Ko, Won Kyu Lee, Sang Taek Jung, Yeon Gyu Yu

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Abstract

G-protein coupled receptors (GPCRs) play indispensable physiological roles in cell proliferation, differentiation, and migration; therefore, identifying the mechanisms by which ligands bind to GPCRs is crucial for developing GPCR-targeting pharmaceutics and for understanding critical biological functions. Although some structural information is available regarding the interactions between GPCRs and their small molecule ligands, knowledge of how GPCRs interact with their corresponding macromolecule ligands, such as peptides and proteins, remains elusive. In this study, we have developed a novel strategy to investigate the precise ligand recognition mechanisms involved in the interaction of endothelin receptor type A (ET_A) with its ligand, endothelin-1 (ET-1); we call this method "directed degeneration" method. Through flow cytometric screening of a randomized ET_A library, statistical analysis of the identified sequences, and biochemical studies, the ligand interaction map was successfully obtained.

Original language	English
Article number	7577
Journal	Scientific reports
Volume	7
Issue number	1
DOIs	https://doi.org/10.1038/s41598-017-08096-6
Publication status	Published - 2017 Dec 1
Externally published	Yes

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title = "Determination of the endothelin-1 recognition sites of endothelin receptor type A by the directed-degeneration method",

abstract = "G-protein coupled receptors (GPCRs) play indispensable physiological roles in cell proliferation, differentiation, and migration; therefore, identifying the mechanisms by which ligands bind to GPCRs is crucial for developing GPCR-targeting pharmaceutics and for understanding critical biological functions. Although some structural information is available regarding the interactions between GPCRs and their small molecule ligands, knowledge of how GPCRs interact with their corresponding macromolecule ligands, such as peptides and proteins, remains elusive. In this study, we have developed a novel strategy to investigate the precise ligand recognition mechanisms involved in the interaction of endothelin receptor type A (ETA) with its ligand, endothelin-1 (ET-1); we call this method {"}directed degeneration{"} method. Through flow cytometric screening of a randomized ETA library, statistical analysis of the identified sequences, and biochemical studies, the ligand interaction map was successfully obtained.",

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AU - Ko, Sanghwan

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AU - Jung, Sang Taek

AU - Yu, Yeon Gyu

PY - 2017/12/1

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AB - G-protein coupled receptors (GPCRs) play indispensable physiological roles in cell proliferation, differentiation, and migration; therefore, identifying the mechanisms by which ligands bind to GPCRs is crucial for developing GPCR-targeting pharmaceutics and for understanding critical biological functions. Although some structural information is available regarding the interactions between GPCRs and their small molecule ligands, knowledge of how GPCRs interact with their corresponding macromolecule ligands, such as peptides and proteins, remains elusive. In this study, we have developed a novel strategy to investigate the precise ligand recognition mechanisms involved in the interaction of endothelin receptor type A (ETA) with its ligand, endothelin-1 (ET-1); we call this method "directed degeneration" method. Through flow cytometric screening of a randomized ETA library, statistical analysis of the identified sequences, and biochemical studies, the ligand interaction map was successfully obtained.

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Determination of the endothelin-1 recognition sites of endothelin receptor type A by the directed-degeneration method

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