Determination of the melanocortin-4 receptor structure identifies Ca 2+ as a cofactor for ligand binding-Reference-Cited by-同舟云学术

Determination of the melanocortin-4 receptor structure identifies Ca 2+ as a cofactor for ligand binding

Published:2020-04-24 Issue:6489 Volume:368 Page:428-433
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Yu Jing¹²³^ORCID,Gimenez Luis E.⁴^ORCID,Hernandez Ciria C.⁴^ORCID,Wu Yiran¹^ORCID,Wein Ariel H.⁵^ORCID,Han Gye Won⁵^ORCID,McClary Kyle⁵,Mittal Sanraj R.⁵,Burdsall Kylie⁵,Stauch Benjamin⁵^ORCID,Wu Lijie¹^ORCID,Stevens Sophia N.¹,Peisley Alys⁴^ORCID,Williams Savannah Y.⁴,Chen Valerie⁶,Millhauser Glenn L.⁶,Zhao Suwen¹²^ORCID,Cone Roger D.⁴⁷^ORCID,Stevens Raymond C.¹²⁵^ORCID

Affiliation:

1. iHuman Institute, ShanghaiTech University, Pudong, Shanghai 201210, China.

2. School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.

3. CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences; University of Chinese Academy of Sciences, Shanghai 200031, China.

4. Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.

5. Departments of Biological Sciences and Chemistry, Bridge Institute, USC Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA.

6. Department of Chemistry and Biochemistry, University of California Santa Cruz, Santa Cruz, CA 95064, USA.

7. Department of Molecular and Integrative Physiology, School of Medicine, University of Michigan, Ann Arbor, MI 48109, USA.

Abstract

Some calcium is required for binding The melanocortin-4 receptor (MC4R) coordinates food intake and energy expenditure and is a target for treating obesity. MC4R is an unusual G protein–coupled receptor, in part because it binds either an endogenous agonist or an endogenous antagonist, leading to reduced appetite or increased food intake, respectively. Yu et al. determined the structure of MC4R bound to an antagonist (see the Perspective by Chaturvedi and Shukla). This structure revealed a calcium ion coordinated by the receptor and the antagonist. Biochemical studies showed that the calcium ion also increased the affinity for endogenous agonist, which translated into increased potency. The authors also confirm a previous finding that MC4R directly couples to the ion channel Kir7.1 and regulates channel gating. Science , this issue p. 428 ; see also p. 369

Funder

National Institutes of Health

European Molecular Biology Organization

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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