2026-05-21T01:07:31Zhttps://keep.lib.asu.edu/oai/requestoai:keep.lib.asu.edu:node-1283622025-09-16T16:34:45Zoai_pmh:alloai_pmh:repo_items128362
https://hdl.handle.net/2286/R.I.44672
<p>Zhang, X., Zhao, F., Wu, Y., Yang, J., Han, G. W., Zhao, S., . . . Xu, F. (2017). Crystal structure of a multi-domain human smoothened receptor in complex with a super stabilizing ligand. Nature Communications, 8, 15383. doi:10.1038/ncomms15383</p>
10.1038/ncomms15383
2041-1723
http://rightsstatements.org/vocab/InC/1.0/
open access
http://creativecommons.org/licenses/by/4.0
2017-05-17
10 pages
eng
Zhang, Xianjun
Zhao, Fei
Wu, Yiran
Yang, Jun
Han, Gye Won
Zhao, Suwen
Ishchenko, Andrii
Ye, Lintao
Lin, Xi
Ding, Kang
Dharmarajan, Venkatasubramaniam
Griffin, Patrick R.
Gati, Cornelius
Nelson, Garrett
Hunter, Mark S.
Hanson, Michael A.
Cherezov, Vadim
Stevens, Raymond C.
Tan, Wenfu
Tao, Houchao
Xu, Fei
College of Liberal Arts and Sciences
The final version of this article, as published in Nature Communications, can be viewed online at: http://www.nature.com/articles/ncomms15383
<p>The Smoothened receptor (SMO) belongs to the Class Frizzled of the G protein-coupled receptor (GPCR) superfamily, constituting a key component of the Hedgehog signalling pathway. Here we report the crystal structure of the multi-domain human SMO, bound and stabilized by a designed tool ligand TC114, using an X-ray free-electron laser source at 2.9 Å. The structure reveals a precise arrangement of three distinct domains: a seven-transmembrane helices domain (TMD), a hinge domain (HD) and an intact extracellular cysteine-rich domain (CRD). This architecture enables allosteric interactions between the domains that are important for ligand recognition and receptor activation. By combining the structural data, molecular dynamics simulation, and hydrogen-deuterium-exchange analysis, we demonstrate that transmembrane helix VI, extracellular loop 3 and the HD play a central role in transmitting the signal employing a unique GPCR activation mechanism, distinct from other multi-domain GPCRs.</p>
Text
Crystal Structure of a Multi-Domain Human Smoothened Receptor in Complex With a Super Stabilizing Ligand