4xee

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Structure of active-like neurotensin receptor

Structural highlights

4xee is a 2 chain structure with sequence from Escherichia virus T4 and Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.9Å
Ligands:1PE, EPE, FLC, PEG
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

NEUT_RAT Neurotensin may play an endocrine or paracrine role in the regulation of fat metabolism. It causes contraction of smooth muscle.

Publication Abstract from PubMed

We previously determined the structure of neurotensin receptor NTSR1 in an active-like conformation with six thermostabilizing mutations bound to the peptide agonist neurotensin. This receptor was unable to activate G proteins, indicating that the mutations restricted NTSR1 to relate agonist binding to G-protein activation. Here we analyse the effect of three of those mutations (E166A(3.49), L310A(6.37), F358A(7.42)) and present two structures of NTSR1 able to catalyse nucleotide exchange at Galpha. The presence of F358(7.42) causes the conserved W321(6.48) to adopt a side chain orientation parallel to the lipid bilayer sealing the collapsed Na(+) ion pocket and linking the agonist with residues in the lower receptor part implicated in GPCR activation. In the intracellular receptor half, the bulkier L310(6.37) side chain dictates the position of R167(3.50) of the highly conserved D/ERY motif. These residues, together with the presence of E166(3.49) provide determinants for G-protein activation by NTSR1.

Structural prerequisites for G-protein activation by the neurotensin receptor.,Krumm BE, White JF, Shah P, Grisshammer R Nat Commun. 2015 Jul 24;6:7895. doi: 10.1038/ncomms8895. PMID:26205105[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations
9 reviews cite this structure
Harnessing Ion-Binding Sites for GPCR Pharmacology.
Zarzycka et al. (2019)
8 more
26 other articles
No citations found

See Also

References

  1. ↑ Krumm BE, White JF, Shah P, Grisshammer R. Structural prerequisites for G-protein activation by the neurotensin receptor. Nat Commun. 2015 Jul 24;6:7895. doi: 10.1038/ncomms8895. PMID:26205105 doi:http://dx.doi.org/10.1038/ncomms8895

Contents


PDB ID 4xee

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