4JKV: Structure of the human smoothened 7TM receptor in complex with an antitumor agent

Citation:
Abstract
The smoothened (SMO) receptor, a key signal transducer in the hedgehog signalling pathway, is responsible for the maintenance of normal embryonic development and is implicated in carcinogenesis. It is classified as a class frizzled (class F) G-protein-coupled receptor (GPCR), although the canonical hedgehog signalling pathway involves the GLI transcription factors and the sequence similarity with class A GPCRs is less than 10%. Here we report the crystal structure of the transmembrane domain of the human SMO receptor bound to the small-molecule antagonist LY2940680 at 2.5 A resolution. Although the SMO receptor shares the seven-transmembrane helical fold, most of the conserved motifs for class A GPCRs are absent, and the structure reveals an unusually complex arrangement of long extracellular loops stabilized by four disulphide bonds. The ligand binds at the extracellular end of the seven-transmembrane-helix bundle and forms extensive contacts with the loops.
PDB ID: 4JKVDownload
MMDB ID: 109459
PDB Deposition Date: 2013/3/11
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 2.45  Å
Source Organism:
Similar Structures:
Biological Unit for 4JKV: dimeric; determined by author and by software (PISA)
Molecular Components in 4JKV
Label Count Molecule
Proteins (2 molecules)
2
Soluble Cytochrome B562, Smoothened Homolog(Gene symbol: SMO)
Molecule annotation
Chemicals (14 molecules)
1
2
2
5
3
3
4
2
5
1
6
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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