A unique hormonal recognition feature of the human glucagon-like peptide-2 receptor

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A unique hormonal recognition feature of the human glucagon-like peptide-2 receptor. / Sun, Wen; Chen, Li-Nan; Zhou, Qingtong; Zhao, Li-Hua; Yang, Dehua; Zhang, Huibing; Cong, Zhaotong; Shen, Dan-Dan; Zhao, Fenghui; Zhou, Fulai; Cai, Xiaoqing; Chen, Yan; Zhou, Yan; Gadgaard, Sarina; van der Velden, Wijnand J. C.; Zhao, Suwen; Jiang, Yi; Rosenkilde, Mette M.; Xu, H. Eric; Zhang, Yan; Wang, Ming-Wei.

I: Cell Research, Bind 30, Nr. 12, 2020, s. 1098-1108.

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

Harvard

Sun, W, Chen, L-N, Zhou, Q, Zhao, L-H, Yang, D, Zhang, H, Cong, Z, Shen, D-D, Zhao, F, Zhou, F, Cai, X, Chen, Y, Zhou, Y, Gadgaard, S, van der Velden, WJC, Zhao, S, Jiang, Y, Rosenkilde, MM, Xu, HE, Zhang, Y & Wang, M-W 2020, 'A unique hormonal recognition feature of the human glucagon-like peptide-2 receptor', Cell Research, bind 30, nr. 12, s. 1098-1108. https://doi.org/10.1038/s41422-020-00442-0

APA

Sun, W., Chen, L-N., Zhou, Q., Zhao, L-H., Yang, D., Zhang, H., Cong, Z., Shen, D-D., Zhao, F., Zhou, F., Cai, X., Chen, Y., Zhou, Y., Gadgaard, S., van der Velden, W. J. C., Zhao, S., Jiang, Y., Rosenkilde, M. M., Xu, H. E., ... Wang, M-W. (2020). A unique hormonal recognition feature of the human glucagon-like peptide-2 receptor. Cell Research, 30(12), 1098-1108. https://doi.org/10.1038/s41422-020-00442-0

Vancouver

Sun W, Chen L-N, Zhou Q, Zhao L-H, Yang D, Zhang H o.a. A unique hormonal recognition feature of the human glucagon-like peptide-2 receptor. Cell Research. 2020;30(12):1098-1108. https://doi.org/10.1038/s41422-020-00442-0

Author

Sun, Wen ; Chen, Li-Nan ; Zhou, Qingtong ; Zhao, Li-Hua ; Yang, Dehua ; Zhang, Huibing ; Cong, Zhaotong ; Shen, Dan-Dan ; Zhao, Fenghui ; Zhou, Fulai ; Cai, Xiaoqing ; Chen, Yan ; Zhou, Yan ; Gadgaard, Sarina ; van der Velden, Wijnand J. C. ; Zhao, Suwen ; Jiang, Yi ; Rosenkilde, Mette M. ; Xu, H. Eric ; Zhang, Yan ; Wang, Ming-Wei. / A unique hormonal recognition feature of the human glucagon-like peptide-2 receptor. I: Cell Research. 2020 ; Bind 30, Nr. 12. s. 1098-1108.

Bibtex

@article{d1b1a26dc67a44f9ab6abc542039f8c3,
title = "A unique hormonal recognition feature of the human glucagon-like peptide-2 receptor",
abstract = "Glucagon-like peptides (GLP-1 and GLP-2) are two proglucagon-derived intestinal hormones that mediate distinct physiological functions through two related receptors (GLP-1R and GLP-2R) which are important drug targets for metabolic disorders and Crohn's disease, respectively. Despite great progress in GLP-1R structure determination, our understanding on the differences of peptide binding and signal transduction between these two receptors remains elusive. Here we report the electron microscopy structure of the human GLP-2R in complex with GLP-2 and a G(s) heterotrimer. To accommodate GLP-2 rather than GLP-1, GLP-2R fine-tunes the conformations of the extracellular parts of transmembrane helices (TMs) 1, 5, 7 and extracellular loop 1 (ECL1). In contrast to GLP-1, the N-terminal histidine of GLP-2 penetrates into the receptor core with a unique orientation. The middle region of GLP-2 engages with TM1 and TM7 more extensively than with ECL2, and the GLP-2 C-terminus closely attaches to ECL1, which is the most protruded among 9 class B G protein-coupled receptors (GPCRs). Functional studies revealed that the above three segments of GLP-2 are essential for GLP-2 recognition and receptor activation, especially the middle region. These results provide new insights into the molecular basis of ligand specificity in class B GPCRs and may facilitate the development of more specific therapeutics.",
keywords = "CRYO-EM STRUCTURE, PROTEIN-COUPLED RECEPTOR, GLP-1 RECEPTOR, STRUCTURAL BASIS, IMMUNOHISTOCHEMICAL DETERMINATION, CRYSTAL-STRUCTURE, ACTIVATION, COMPLEX, BINDING, DOMAIN",
author = "Wen Sun and Li-Nan Chen and Qingtong Zhou and Li-Hua Zhao and Dehua Yang and Huibing Zhang and Zhaotong Cong and Dan-Dan Shen and Fenghui Zhao and Fulai Zhou and Xiaoqing Cai and Yan Chen and Yan Zhou and Sarina Gadgaard and {van der Velden}, {Wijnand J. C.} and Suwen Zhao and Yi Jiang and Rosenkilde, {Mette M.} and Xu, {H. Eric} and Yan Zhang and Ming-Wei Wang",
year = "2020",
doi = "10.1038/s41422-020-00442-0",
language = "English",
volume = "30",
pages = "1098--1108",
journal = "Cell Research",
issn = "1001-0602",
publisher = "nature publishing group",
number = "12",

}

RIS

TY - JOUR

T1 - A unique hormonal recognition feature of the human glucagon-like peptide-2 receptor

AU - Sun, Wen

AU - Chen, Li-Nan

AU - Zhou, Qingtong

AU - Zhao, Li-Hua

AU - Yang, Dehua

AU - Zhang, Huibing

AU - Cong, Zhaotong

AU - Shen, Dan-Dan

AU - Zhao, Fenghui

AU - Zhou, Fulai

AU - Cai, Xiaoqing

AU - Chen, Yan

AU - Zhou, Yan

AU - Gadgaard, Sarina

AU - van der Velden, Wijnand J. C.

AU - Zhao, Suwen

AU - Jiang, Yi

AU - Rosenkilde, Mette M.

AU - Xu, H. Eric

AU - Zhang, Yan

AU - Wang, Ming-Wei

PY - 2020

Y1 - 2020

N2 - Glucagon-like peptides (GLP-1 and GLP-2) are two proglucagon-derived intestinal hormones that mediate distinct physiological functions through two related receptors (GLP-1R and GLP-2R) which are important drug targets for metabolic disorders and Crohn's disease, respectively. Despite great progress in GLP-1R structure determination, our understanding on the differences of peptide binding and signal transduction between these two receptors remains elusive. Here we report the electron microscopy structure of the human GLP-2R in complex with GLP-2 and a G(s) heterotrimer. To accommodate GLP-2 rather than GLP-1, GLP-2R fine-tunes the conformations of the extracellular parts of transmembrane helices (TMs) 1, 5, 7 and extracellular loop 1 (ECL1). In contrast to GLP-1, the N-terminal histidine of GLP-2 penetrates into the receptor core with a unique orientation. The middle region of GLP-2 engages with TM1 and TM7 more extensively than with ECL2, and the GLP-2 C-terminus closely attaches to ECL1, which is the most protruded among 9 class B G protein-coupled receptors (GPCRs). Functional studies revealed that the above three segments of GLP-2 are essential for GLP-2 recognition and receptor activation, especially the middle region. These results provide new insights into the molecular basis of ligand specificity in class B GPCRs and may facilitate the development of more specific therapeutics.

AB - Glucagon-like peptides (GLP-1 and GLP-2) are two proglucagon-derived intestinal hormones that mediate distinct physiological functions through two related receptors (GLP-1R and GLP-2R) which are important drug targets for metabolic disorders and Crohn's disease, respectively. Despite great progress in GLP-1R structure determination, our understanding on the differences of peptide binding and signal transduction between these two receptors remains elusive. Here we report the electron microscopy structure of the human GLP-2R in complex with GLP-2 and a G(s) heterotrimer. To accommodate GLP-2 rather than GLP-1, GLP-2R fine-tunes the conformations of the extracellular parts of transmembrane helices (TMs) 1, 5, 7 and extracellular loop 1 (ECL1). In contrast to GLP-1, the N-terminal histidine of GLP-2 penetrates into the receptor core with a unique orientation. The middle region of GLP-2 engages with TM1 and TM7 more extensively than with ECL2, and the GLP-2 C-terminus closely attaches to ECL1, which is the most protruded among 9 class B G protein-coupled receptors (GPCRs). Functional studies revealed that the above three segments of GLP-2 are essential for GLP-2 recognition and receptor activation, especially the middle region. These results provide new insights into the molecular basis of ligand specificity in class B GPCRs and may facilitate the development of more specific therapeutics.

KW - CRYO-EM STRUCTURE

KW - PROTEIN-COUPLED RECEPTOR

KW - GLP-1 RECEPTOR

KW - STRUCTURAL BASIS

KW - IMMUNOHISTOCHEMICAL DETERMINATION

KW - CRYSTAL-STRUCTURE

KW - ACTIVATION

KW - COMPLEX

KW - BINDING

KW - DOMAIN

U2 - 10.1038/s41422-020-00442-0

DO - 10.1038/s41422-020-00442-0

M3 - Journal article

C2 - 33239759

VL - 30

SP - 1098

EP - 1108

JO - Cell Research

JF - Cell Research

SN - 1001-0602

IS - 12

ER -

ID: 257024541