Structural insights into ligand recognition and activation of the melanocortin-4 receptor.

Amino Acid Sequence Humans Ligands Obesity Receptor, Melanocortin, Type 4 / chemistry

Journal

Cell research
ISSN: 1748-7838
Titre abrégé: Cell Res
Pays: England
ID NLM: 9425763

Informations de publication

Date de publication:
11 2021
Historique:
received: 22 05 2021
accepted: 27 07 2021
pubmed: 27 8 2021
medline: 27 1 2022
entrez: 26 8 2021
Statut: ppublish

Résumé

Melanocortin-4 receptor (MC4R) plays a central role in the regulation of energy homeostasis. Its high sequence similarity to other MC receptor family members, low agonist selectivity and the lack of structural information concerning MC4R-specific activation have hampered the development of MC4R-seletive therapeutics to treat obesity. Here, we report four high-resolution structures of full-length MC4R in complex with the heterotrimeric G

Identifiants

DOI: 10.1038/s41422-021-00552-3 PMID: 34433901 PMC: PMC8563965
pubmed: 34433901
doi: 10.1038/s41422-021-00552-3
pii: 10.1038/s41422-021-00552-3
pmc: PMC8563965
doi:

Substances chimiques

Ligands 0
MC4R protein, human 0
Receptor, Melanocortin, Type 4 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1163-1175

Commentaires et corrections

Type : CommentIn

Informations de copyright

© 2021. The Author(s), under exclusive licence to Center for Excellence in Molecular Cell Science, CAS.

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Auteurs

Huibing Zhang (H)

Department of Biophysics and Department of Pathology of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, Zhejiang, China.
MOE Frontier Science Center for Brain Research and Brain-Machine Integration, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Key Laboratory of Immunity and Inflammatory Diseases of Zhejiang Province, Hangzhou, Zhejiang, China.

Li-Nan Chen (LN)

Department of Biophysics and Department of Pathology of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, Zhejiang, China.
MOE Frontier Science Center for Brain Research and Brain-Machine Integration, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Key Laboratory of Immunity and Inflammatory Diseases of Zhejiang Province, Hangzhou, Zhejiang, China.

Dehua Yang (D)

The CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
University of Chinese Academy of Sciences, Beijing, China.
ORCID: 0000-0003-3028-3243

Chunyou Mao (C)

Department of Biophysics and Department of Pathology of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, Zhejiang, China.
MOE Frontier Science Center for Brain Research and Brain-Machine Integration, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Key Laboratory of Immunity and Inflammatory Diseases of Zhejiang Province, Hangzhou, Zhejiang, China.
ORCID: 0000-0001-5349-8592

Qingya Shen (Q)

Department of Biophysics and Department of Pathology of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, Zhejiang, China.
MOE Frontier Science Center for Brain Research and Brain-Machine Integration, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Key Laboratory of Immunity and Inflammatory Diseases of Zhejiang Province, Hangzhou, Zhejiang, China.
ORCID: 0000-0001-6602-7116

Wenbo Feng (W)

School of Pharmacy, Fudan University, Shanghai, China.

Dan-Dan Shen (DD)

Department of Biophysics and Department of Pathology of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, Zhejiang, China.
MOE Frontier Science Center for Brain Research and Brain-Machine Integration, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Key Laboratory of Immunity and Inflammatory Diseases of Zhejiang Province, Hangzhou, Zhejiang, China.
ORCID: 0000-0001-8757-4602

Antao Dai (A)

The CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.

Shanshan Xie (S)

Department of Cell Biology and Cancer Institute of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Institute of Gastroenterology, Zhejiang University, Hangzhou, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang, China; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
ORCID: 0000-0003-4294-8169

Yan Zhou (Y)

The CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.

Jiao Qin (J)

Department of Biophysics and Department of Pathology of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, Zhejiang, China.
MOE Frontier Science Center for Brain Research and Brain-Machine Integration, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Key Laboratory of Immunity and Inflammatory Diseases of Zhejiang Province, Hangzhou, Zhejiang, China.

Jin-Peng Sun (JP)

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China.
Key Laboratory Experimental Teratology of the Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.

Daniel H Scharf (DH)

Department of Microbiology and The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

Tingjun Hou (T)

Innovation Institute for Artificial Intelligence in Medicine of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China.

Tianhua Zhou (T)

Department of Cell Biology and Cancer Institute of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Institute of Gastroenterology, Zhejiang University, Hangzhou, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang, China; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.

Ming-Wei Wang (MW)

The CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China. mwwang@simm.ac.cn.
The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China. mwwang@simm.ac.cn.
University of Chinese Academy of Sciences, Beijing, China. mwwang@simm.ac.cn.
School of Pharmacy, Fudan University, Shanghai, China. mwwang@simm.ac.cn.
School of Life Science and Technology, ShanghaiTech University, Shanghai, China. mwwang@simm.ac.cn.
Department of Pharmacology, Fudan University, Shanghai, China. mwwang@simm.ac.cn.
ORCID: 0000-0001-6550-9017

Yan Zhang (Y)

Department of Biophysics and Department of Pathology of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. zhang_yan@zju.edu.cn.
Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, Zhejiang, China. zhang_yan@zju.edu.cn.
MOE Frontier Science Center for Brain Research and Brain-Machine Integration, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. zhang_yan@zju.edu.cn.
Key Laboratory of Immunity and Inflammatory Diseases of Zhejiang Province, Hangzhou, Zhejiang, China. zhang_yan@zju.edu.cn.
ORCID: 0000-0003-2189-0244

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Classifications MeSH

questionsmedicales.fr › Sciences de l'information › Sources d'information › Services d'information › Documentation › Données de séquences moléculaires › Séquence d'acides aminés › Structural insights into ligand recognition...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Structural insights into ligand recognition...
questionsmedicales.fr › Actions chimiques et utilisations › Utilisations spécialisées de produits chimiques › Produits chimiques de laboratoire › Ligands › Structural insights into ligand recognition...
questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Obésité › Structural insights into ligand recognition...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs peptidiques › Récepteur hormone hypophysaire › Récepteur corticotrophine › Récepteurs à la mélanocortine › Récepteur de la mélanocortine de type 4 › Structural insights into ligand recognition...