Neurotensin receptor

Neurotensin receptors are transmembrane receptors that bind the neurotransmitter neurotensin.[1][2] Two of the receptors encoded by the NTSR1 and NTSR2 genes contain seven transmembrane helices and are G protein coupled. Numerous crystal structures have been reported for the neurotensin receptor 1 (NTS1).[3] The third receptor has a single transmembrane domain and is encoded by the SORT1 gene.

neurotensin receptor 1 (high affinity)
Identifiers
SymbolNTSR1
Alt. symbolsNTR
NCBI gene4923
HGNC8039
OMIM162651
RefSeqNM_002531
UniProtP30989
Other data
LocusChr. 20 q13-20q13
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StructuresSwiss-model
DomainsInterPro
neurotensin receptor 2
Identifiers
SymbolNTSR2
Alt. symbolsNTR2
NCBI gene23620
HGNC8040
OMIM605538
RefSeqNM_012344
UniProtO95665
Other data
LocusChr. 2 p25.1
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StructuresSwiss-model
DomainsInterPro
sortilin 1
Identifiers
SymbolSORT1
Alt. symbolsGp95, NT3
NCBI gene6272
HGNC11186
OMIM602458
RefSeqNM_002959
UniProtQ99523
Other data
LocusChr. 1 p21.3-1p13.1
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StructuresSwiss-model
DomainsInterPro

Ligands

Agonists
Peptide
  • Beta-lactotensin (NTS2)[4]
  • JMV-449
  • Neurotensin
  • Neuromedin N (NTS1 selective)
  • PD-149,163 (NTS1 selective, reduced amide bond 8-13 fragment of neurotensin)
Non-peptide
  • NTS1 full agonist SRI-9829 [3]
  • Partial agonists derived from SR-48692[5]

Antagonists

Biophysical Investigation

Unusually for GPCRs, NTS1 can be expressed in an active form in the bacteria E. coli.[8] It can be purified and analysed in vitro and has been analysed by a number of biophysical techniques such as surface plasmon resonance,[9] FRET[10] and cryo-electron microscopy.[11] Furthermore, high-resolution crystal structures of NTS1 have been determined in complex with the peptide full agonist NT8-13, the non-peptide full agonist SRI-9829, the partial agonist RTI-3a, and the antagonists / inverse agonists SR-48692 and SR-142948, as well as in the ligand-free apo state [3]

References
  1. Vincent JP, Mazella J, Kitabgi P (1999). "Neurotensin and neurotensin receptors". Trends Pharmacol. Sci. 20 (7): 302–309. doi:10.1016/S0165-6147(99)01357-7. PMID 10390649.
  2. Pelaprat D (2006). "Interactions between neurotensin receptors and G proteins". Peptides. 27 (10): 2476–2487. doi:10.1016/j.peptides.2006.04.027. PMID 16919370. S2CID 21730838.
  3. Deluigi M, Klipp A, Klenk C, Merklinger L, Eberle SA, Morstein L, Heine P, Mittl PR, Ernst P, Kamenecka TM, He Y, Vacca S, Egloff P, Honegger A, Plückthun A (January 2021). "Complexes of the neurotensin receptor 1 with small-molecule ligands reveal structural determinants of full, partial, and inverse agonism". Science Advances. 7 (5): eabe5504. Bibcode:2021SciA....7.5504D. doi:10.1126/sciadv.abe5504. PMC 7840143. PMID 33571132.
  4. Yamauchi R, Usui H, Yunden J, Takenaka Y, Tani F, Yoshikawa M (April 2003). "Characterization of beta-lactotensin, a bioactive peptide derived from bovine beta-lactoglobulin, as a neurotensin agonist". Bioscience, Biotechnology, and Biochemistry. 67 (4): 940–3. doi:10.1271/bbb.67.940. PMID 12784648. S2CID 83609327.
  5. Thomas JB, Navarro H, Warner KR, Gilmour B (March 2009). "The identification of nonpeptide neurotensin receptor partial agonists from the potent antagonist SR48692 using a calcium mobilization assay". Bioorganic & Medicinal Chemistry Letters. 19 (5): 1438–1441. doi:10.1016/j.bmcl.2009.01.024. PMC 4418176. PMID 19195889.
  6. Bredeloux P, Costentin J, Dubuc I (December 2006). "Interactions between NTS2 neurotensin and opioid receptors on two nociceptive responses assessed on the hot plate test in mice". Behavioural Brain Research. 175 (2): 399–407. doi:10.1016/j.bbr.2006.09.016. PMID 17074405. S2CID 24790151.
  7. Ferraro L, Tomasini MC, Mazza R, Fuxe K, Fournier J, Tanganelli S, Antonelli T (August 2008). "Neurotensin receptors as modulators of glutamatergic transmission". Brain Research Reviews. 58 (2): 365–373. doi:10.1016/j.brainresrev.2007.11.001. PMID 18096238. S2CID 25434443.
  8. Attrill H, Harding PJ, Smith E, Ross S, Watts A (2009). "Improved yield of a ligand-binding GPCR expressed in E. coli for structural studies". Protein Expr Purif. 64 (1): 32–38. doi:10.1016/j.pep.2008.10.001. PMID 18976711.
  9. Harding PJ, Hadingham TC, McDonnell JM, Watts A (2006). "Direct analysis of a GPCR-agonist interaction by surface plasmon resonance". Eur Biophys J. 35 (8): 709–712. doi:10.1007/s00249-006-0070-x. PMID 16708210. S2CID 7844675.
  10. Harding PJ, Attrill H, Boehringer J, Ross S, Wadhams GH, Smith E, Armitage JP, Watts A (2009). "Constitutive dimerization of the G-protein coupled receptor, neurotensin receptor 1, reconstituted into phospholipid bilayers". Biophys. J. 96 (3): 964–973. Bibcode:2009BpJ....96..964H. doi:10.1016/j.bpj.2008.09.054. PMC 2716571. PMID 19186134.
  11. Selmi DN, Adamson RJ, Attrill H, Goddard AD, Gilbert RJ, Watts A, Turberfield AJ (2011). "DNA-templated protein arrays for single-molecule imaging". Nano Lett. 11 (2): 657–660. Bibcode:2011NanoL..11..657S. doi:10.1021/nl1037769. PMID 21218848.


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