5v57
From Proteopedia
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/SMO_HUMAN SMO_HUMAN]] G protein-coupled receptor that probably associates with the patched protein (PTCH) to transduce the hedgehog's proteins signal. Binding of sonic hedgehog (SHH) to its receptor patched is thought to prevent normal inhibition by patched of smoothened (SMO). Required for the accumulation of KIF7 and GLI3 in the cilia.<ref>PMID:19592253</ref> | [[http://www.uniprot.org/uniprot/SMO_HUMAN SMO_HUMAN]] G protein-coupled receptor that probably associates with the patched protein (PTCH) to transduce the hedgehog's proteins signal. Binding of sonic hedgehog (SHH) to its receptor patched is thought to prevent normal inhibition by patched of smoothened (SMO). Required for the accumulation of KIF7 and GLI3 in the cilia.<ref>PMID:19592253</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | 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 A. 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. | ||
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| + | Crystal structure of a multi-domain human smoothened receptor in complex with a super stabilizing ligand.,Zhang X, Zhao F, Wu Y, Yang J, Han GW, Zhao S, Ishchenko A, Ye L, Lin X, Ding K, Dharmarajan V, Griffin PR, Gati C, Nelson G, Hunter MS, Hanson MA, Cherezov V, Stevens RC, Tan W, Tao H, Xu F Nat Commun. 2017 May 17;8:15383. doi: 10.1038/ncomms15383. PMID:28513578<ref>PMID:28513578</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5v57" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 09:43, 3 August 2017
3.0A SYN structure of the multi-domain human smoothened receptor in complex with TC114
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Categories: Cherezov, V | Dharmarajan, V | Ding, K | Gati, C | Griffin, P R | Han, G W | Hanson, M A | Hunter, M S | Ishchenko, A | Lin, X | Nelson, G | Stevens, R C | Tan, W | Tao, H | Wu, Y | Xu, F | Yang, J | Ye, L | Zhang, X | Zhao, F | Zhao, S | 7tm domain | Class f | Extracellular cystein-rich domain | Flavodoxin | Gpcr | Gpcr hedgehog signaling | Hinge domain | Human smoothened receptor complex | Lcp | Membrane protein | Synchrotron radiation | Tc114
