Neurotensin receptor
Topic: Biology
From HandWiki - Reading time: 6 min
| Neurotensin receptor 1 (high affinity) | |
|---|---|
 3D structure model of the neurotensin receptor NTS1 in complex with NTS(8-13) based on PDB 4GRV | |
| Identifiers | |
| Symbol | NTSR1 |
| Alt. symbols | NTR |
| NCBI gene | 4923 |
| HGNC | 8039 |
| OMIM | 162651 |
| RefSeq | NM_002531 |
| UniProt | P30989 |
| Other data | |
| Locus | Chr. 20 q13-20q13 |
| Neurotensin receptor 2 | |
|---|---|
| Identifiers | |
| Symbol | NTSR2 |
| Alt. symbols | NTR2 |
| NCBI gene | 23620 |
| HGNC | 8040 |
| OMIM | 605538 |
| RefSeq | NM_012344 |
| UniProt | O95665 |
| Other data | |
| Locus | Chr. 2 p25.1 |
| Sortilin 1 | |
|---|---|
| Identifiers | |
| Symbol | SORT1 |
| Alt. symbols | Gp95, NT3 |
| NCBI gene | 6272 |
| HGNC | 11186 |
| OMIM | 602458 |
| RefSeq | NM_002959 |
| UniProt | Q99523 |
| Other data | |
| Locus | Chr. 1 p21.3-1p13.1 |
Neurotensin receptors are transmembrane receptors that bind the neurotransmitter neurotensin.[1][2] Two of the receptors encoded by the NTSR1 and NTSR2 genes are G protein-coupled receptors, while the third receptor, called NTS3 or Sortilin, is a single transmembrane domain receptor encoded by the gene SORT1.[3] It is a multi-functional protein which also participates in protein sorting.[3] NTSR1’s function is mediated by its binding to Gq alpha subunit family G-proteins, while NTSR2’s signaling pathway is not yet fully understood.[3]
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
Antagonists
- Levocabastine (NTS2 selective, also H1 histamine antagonist)[7]
- SR-48692 (NTS1 selective)[8]
- SR-142948 (unselective, CAS# 184162-64-9)
Biophysical investigation
Unusually for GPCRs, NTS1 can be expressed in an active form in the bacteria E. coli.[9] It can be purified and analysed in vitro and has been analysed by a number of biophysical techniques such as surface plasmon resonance,[10] FRET[11] and cryo-electron microscopy.[12] 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 [5]
References
- ↑ "Neurotensin and neurotensin receptors". Trends Pharmacol. Sci. 20 (7): 302–309. 1999. doi:10.1016/S0165-6147(99)01357-7. PMID 10390649.
- ↑ 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. https://www.hal.inserm.fr/inserm-00519739/document.
- ↑ 3.0 3.1 3.2 "Neurotensin pathway in digestive cancers and clinical applications: an overview". Cell Death & Disease 11 (12). 2020-12-02. doi:10.1038/s41419-020-03245-8. PMID 33268796.
- ↑ "Characterization of beta-lactotensin, a bioactive peptide derived from bovine beta-lactoglobulin, as a neurotensin agonist". Bioscience, Biotechnology, and Biochemistry 67 (4): 940–3. April 2003. doi:10.1271/bbb.67.940. PMID 12784648. http://joi.jlc.jst.go.jp/JST.JSTAGE/bbb/67.940?lang=en&from=PubMed.
- ↑ 5.0 5.1 "Complexes of the neurotensin receptor 1 with small-molecule ligands reveal structural determinants of full, partial, and inverse agonism". Science Advances 7 (5). January 2021. doi:10.1126/sciadv.abe5504. PMID 33571132. Bibcode: 2021SciA....7.5504D.
- ↑ "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. March 2009. doi:10.1016/j.bmcl.2009.01.024. PMID 19195889.
- ↑ "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. December 2006. doi:10.1016/j.bbr.2006.09.016. PMID 17074405.
- ↑ "Neurotensin receptors as modulators of glutamatergic transmission". Brain Research Reviews 58 (2): 365–373. August 2008. doi:10.1016/j.brainresrev.2007.11.001. PMID 18096238.
- ↑ "Improved yield of a ligand-binding GPCR expressed in E. coli for structural studies.". Protein Expr Purif 64 (1): 32–38. 2009. doi:10.1016/j.pep.2008.10.001. PMID 18976711.
- ↑ "Direct analysis of a GPCR-agonist interaction by surface plasmon resonance.". Eur Biophys J 35 (8): 709–712. 2006. doi:10.1007/s00249-006-0070-x. PMID 16708210.
- ↑ "Constitutive dimerization of the G-protein coupled receptor, neurotensin receptor 1, reconstituted into phospholipid bilayers.". Biophys. J. 96 (3): 964–973. 2009. doi:10.1016/j.bpj.2008.09.054. PMID 19186134. Bibcode: 2009BpJ....96..964H.
- ↑ "DNA-templated protein arrays for single-molecule imaging.". Nano Lett. 11 (2): 657–660. 2011. doi:10.1021/nl1037769. PMID 21218848. Bibcode: 2011NanoL..11..657S. https://figshare.com/articles/journal_contribution/24403630.
External links
- "Neurotensin Receptors". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. http://www.iuphar-db.org/GPCR/ChapterMenuForward?chapterID=1342.
- Neurotensin+Receptors at the US National Library of Medicine Medical Subject Headings (MeSH)
 |  |
EncycloReader
is supported by the 
KSF