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

Jing Yu | Zendy; Luis E. Gimenez | Zendy; Ciria C. Hernández | Zendy; Yiran Wu | Zendy; Ariel H. Wein | Zendy; Gye Won Han | Zendy; Kyle M. McClary | Zendy; Sanraj R. Mittal | Zendy; Kylie Burdsall | Zendy; Benjamin Stauch | Zendy; Lijie Wu | Zendy; Sophia N. Stevens | Zendy; Alys Peisley | Zendy; Savannah Y. Williams | Zendy; Valerie Chen | Zendy; Glenn L. Millhauser | Zendy; Suwen Zhao | Zendy; Roger D. Cone | Zendy; Raymond C. Stevens | Zendy

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

Author(s) -

Jing Yu,

Luis E. Gimenez,

Ciria C. Hernández,

Yiran Wu,

Ariel H. Wein,

Gye Won Han,

Kyle M. McClary,

Sanraj R. Mittal,

Kylie Burdsall,

Benjamin Stauch,

Lijie Wu,

Sophia N. Stevens,

Alys Peisley,

Savannah Y. Williams,

Valerie Chen,

Glenn L. Millhauser,

Suwen Zhao,

Roger D. Cone,

Raymond C. Stevens

Publication year - 2020

Publication title -

science

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 12.556

H-Index - 1186

eISSN - 1095-9203

pISSN - 0036-8075

DOI - 10.1126/science.aaz8995

Subject(s) - agonist , chemistry , antagonist , receptor , endocrinology , endogeny , endogenous agonist , medicine , melanocortin 4 receptor , melanocortin , biochemistry , biology , dopamine receptor d1

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. Yuet 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

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