Determination of the melanocortin-4 receptor structure identifies Ca2+ as a cofactor for ligand binding.

Journal: Science

Published: 2020-04-24

DOI: 10.1126/science.aaz8995

Affiliations: 14

Authors: 19

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Research Highlight

Brain protein structure solved

© Planet Flem/Getty

© Planet Flem/Getty

The discovery of the precise shape of a brain protein could lead to more-effective drugs for obesity.

A team co-led by scientists at ShanghaiTech University solved the atomic structure of the melanocortin-4 receptor (MC4R), a protein found in the brain that regulates hunger cues and the body’s energy balance.

Unexpectedly, the researchers identified a binding site for calcium on MC4R — a feature not seen with other proteins in the melanocortin receptor family. The team further detailed how calcium binding impacts the affinity of MC4R for neuropeptides that influence downstream signalling.

A drug that activates MC4R is already available for people with rare genetic forms of syndromic obesity, but it is not potent enough to treat more-common, diet-associated forms of obesity. The new structural insights into MC4R could open the door to novel drug designs that can help manage weight problems more broadly.

Supported content

  1. Science 368, 428–433 (2020). doi: 10.1126/science.aaz8995
Institutions Share
Life Sciences Institute (LSI), U-M, United States of America (USA) 0.24
iHuman Institute, ShanghaiTech, China 0.20
USC Department of Biological Sciences, United States of America (USA) 0.18
Department of Chemistry and Biochemistry, UCSC, United States of America (USA) 0.11
USC Bridge Institute, United States of America (USA) 0.09
USC Michelson Center for Convergent Bioscience, United States of America (USA) 0.09
School of Life Science and Technology (SLST), ShanghaiTech, China 0.05
Department of Molecular and Integrative Physiology, U-M, United States of America (USA) 0.03
CAS Center for Excellence in Molecular Cell Science, SIBS CAS, China 0.01
Institute of Biochemistry and Cell Biology (IBCB), SIBS CAS, China 0.01
University of Chinese Academy of Sciences (UCAS), Shanghai, China 0.01