 |
PDBsum entry 4or2
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Signaling protein
|
PDB id
|
|
|
|
4or2
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Structure of a class c gpcr metabotropic glutamate receptor 1 bound to an allosteric modulator.
|
|
|
Authors
|
|
H.Wu,
C.Wang,
K.J.Gregory,
G.W.Han,
H.P.Cho,
Y.Xia,
C.M.Niswender,
V.Katritch,
J.Meiler,
V.Cherezov,
P.J.Conn,
R.C.Stevens.
|
|
|
Ref.
|
|
Science, 2014,
344,
58-64.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
Abstract
|
|
|
The excitatory neurotransmitter glutamate induces modulatory actions via the
metabotropic glutamate receptors (mGlus), which are class C G protein-coupled
receptors (GPCRs). We determined the structure of the human mGlu1 receptor
seven-transmembrane (7TM) domain bound to a negative allosteric modulator, FITM,
at a resolution of 2.8 angstroms. The modulator binding site partially overlaps
with the orthosteric binding sites of class A GPCRs but is more restricted than
most other GPCRs. We observed a parallel 7TM dimer mediated by cholesterols,
which suggests that signaling initiated by glutamate's interaction with the
extracellular domain might be mediated via 7TM interactions within the
full-length receptor dimer. A combination of crystallography, structure-activity
relationships, mutagenesis, and full-length dimer modeling provides insights
about the allosteric modulation and activation mechanism of class C GPCRs.
|
|
|
|
|
|
|
