4XEE

Structure of active-like neurotensin receptor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.90 Å
  • R-Value Free: 0.281 
  • R-Value Work: 0.231 
  • R-Value Observed: 0.234 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Structural prerequisites for G-protein activation by the neurotensin receptor.

Krumm, B.E.White, J.F.Shah, P.Grisshammer, R.

(2015) Nat Commun 6: 7895-7895

  • DOI: https://doi.org/10.1038/ncomms8895
  • Primary Citation of Related Structures:  
    4XEE, 4XES

  • 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.


  • Organizational Affiliation

    Membrane Protein Structure Function Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Department of Health and Human Services, 5625 Fishers Lane, Rockville, Maryland 20852, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Neurotensin receptor type 1, Endolysin chimera541Rattus norvegicusTequatrovirus T4
This entity is chimeric
Mutation(s): 3 
Gene Names: Ntsr1Ntsr
EC: 3.2.1.17
Membrane Entity: Yes 
UniProt
Find proteins for P20789 (Rattus norvegicus)
Explore P20789 
Go to UniProtKB:  P20789
Find proteins for P00720 (Enterobacteria phage T4)
Explore P00720 
Go to UniProtKB:  P00720
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupsP20789P00720
Sequence Annotations
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  • Reference Sequence

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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Neurotensin/neuromedin N6Rattus norvegicusMutation(s): 0 
Membrane Entity: Yes 
UniProt
Find proteins for P20068 (Rattus norvegicus)
Explore P20068 
Go to UniProtKB:  P20068
Entity Groups  
UniProt GroupP20068
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.90 Å
  • R-Value Free: 0.281 
  • R-Value Work: 0.231 
  • R-Value Observed: 0.234 
  • Space Group: P 21 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 49.07α = 90
b = 88.11β = 90
c = 161.29γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
XDSdata reduction
XSCALEdata scaling
PHASERphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2015-07-29
    Type: Initial release
  • Version 1.1: 2015-08-05
    Changes: Database references
  • Version 1.2: 2019-11-27
    Changes: Advisory, Author supporting evidence, Derived calculations
  • Version 1.3: 2023-09-27
    Changes: Advisory, Data collection, Database references, Refinement description