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

被引：5

作者：

Han, Seong-Gu ^{[1
]}

Ko, Sanghwan ^{[1
]}

Lee, Won-Kyu ^{[1
,2
]}

Jung, Sang Taek ^{[1
]}

Yu, Yeon Gyu ^{[1
]}

机构：

[1] Kookmin Univ, Dept Chem, 861-1 Jeongneung Dong, Seoul 136702, South Korea

[2] Osong Med Innovat Fdn, New Drug Dev Ctr, Osong Sengmyung Ro 123, Cheongju, Chungbuk, South Korea

来源：

SCIENTIFIC REPORTS | 2017年 / 7卷

基金：

新加坡国家研究基金会;

关键词：

DRUG DESIGN; LIGAND; THERMODYNAMICS; ANTAGONIST; SUBTYPES; ETA;

D O I：

10.1038/s41598-017-08096-6

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：9

共 37 条

[1] IDENTIFICATION OF A LIGAND-BINDING SITE OF THE HUMAN ENDOTHELIN-A RECEPTOR AND SPECIFIC REGIONS REQUIRED FOR LIGAND SELECTIVITY [J].