4XEE

Structure of active-like neurotensin receptor

Summary for 4XEE

• Entry DOI: 10.2210/pdb4xee/pdb
• Related: 4XES
• Descriptor: Neurotensin receptor type 1, Endolysin chimera, Neurotensin/neuromedin N, PENTAETHYLENE GLYCOL, ... (7 entities in total)
• Functional Keywords: membrane protein, g protein-coupled receptor, gpcr, neurotensin receptor, ntsr1, signaling protein, hydrolase
• Biological source: Rattus norvegicus (Rat); More
• Total number of polymer chains: 2
• Total formula weight: 62572.93

Authors

Krumm, B.E.,White, J.F.,Shah, P.,Grisshammer, R. (deposition date: 2014-12-23, release date: 2015-07-29, Last modification date: 2024-11-06)

Primary citation

Krumm, B.E.,White, J.F.,Shah, P.,Grisshammer, R.
Structural prerequisites for G-protein activation by the neurotensin receptor.
Nat Commun, 6:7895-7895, 2015

PubMed Abstract: 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 Gα. 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.

PubMed: 26205105
DOI: 10.1038/ncomms8895

Experimental method

X-RAY DIFFRACTION (2.9 Å)