Crystal structure of the Frizzled 4 receptor in a ligand-free state

Journal: Nature

Published: 2018-08-22

DOI: 10.1038/s41586-018-0447-x

Affiliations: 11

Authors: 25

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Research Highlight

Frazzled by Frizzled no more!

© LAGUNA DESIGN/Getty

© LAGUNA DESIGN/Getty

A family of protein receptors known as Frizzled plays an integral role in cancer development, but targeting them with drugs has proven difficult owing to the lack of structural information.

Now, a team led by researchers from ShanghaiTech University has deciphered the high-resolution crystal structure of the first human Frizzled receptor — FZD4 — an advance that could open new possibilities in cancer therapeutics.

The researchers described an unusual protein architecture in which the binding pocket of FZD4 is narrow with limited accessibility to other molecules. This conformation is conserved across all other Frizzled receptors, too.

That observation could help explain why solving the structure proved elusive for so long. The unique design of Frizzled receptors may also require a unique approach to drug discovery, the researchers advise.

Supported content

  1. Nature 560, 666–670 (2018). doi: 10.1038/s41586-018-0447-x
Institutions FC
iHuman Institute, ShanghaiTech, China 0.27
Center for Cancer and Cell Biology, VAI, United States of America (USA) 0.21
USC Bridge Institute, United States of America (USA) 0.12
School of Life Science and Technology (SLST), ShanghaiTech, China 0.11
Center for Life Sciences, HIT, China 0.08
Mayo Clinic Department of Molecular Pharmacology and Experimental Therapeutics, United States of America (USA) 0.08
Moscow Institute of Physics and Technology - State University (MIPT), Russia 0.04
Institute of Biochemistry and Cell Biology (IBCB), SIBS CAS, China 0.03
University of Chinese Academy of Sciences (UCAS), China 0.03
CAS Key Laboratory of Receptor Research (CASKLRR), SIMM CAS, China 0.01
VARI/SIMM Center, United States of America (USA) 0.01

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