Sandbox Reserved 1176: Difference between revisions

    

==Introduction==

Neurotensin receptor 1 (NTSR1) is a '''[https://en.wikipedia.org/wiki/G_protein%E2%80%93coupled_receptor G-protein coupled receptor (GPCR).]''' GPCRs are a class of proteins with an extracellular binding domain and 7 transmembrane helices found only in '''[https://en.wikipedia.org/wiki/Eukaryote. eukaryotes]''' that assist in propagating a cellular response. This is accomplished by the binding of molecules to the GPCR outside the cell,causing a '''[https://en.wikipedia.org/wiki/Conformational_change conformational change]''' and activating a '''[https://en.wikipedia.org/wiki/Signal_transduction signal transduction]''' pathway via '''[https://en.wikipedia.org/wiki/Second_messenger_system second messengers]''' such as '''[https://en.wikipedia.org/wiki/Cyclic_adenosine_monophosphate  cyclic AMP]''', '''[https://en.wikipedia.org/wiki/Inositol_trisphosphate  inositol triphosphate]''', and '''[https://en.wikipedia.org/wiki/Diglyceride  diacylglycerol]'''.<ref name="SPGP"/>. NTSR1 binds to the 13 amino acid peptide, neurotensin (NTS)<ref name="SONT">PMID:23051748</ref>, and the majority of the effects of NTS are mediated through NTSR1<ref name="SONT"/>. NTS has a variety of biological activities including a role in the '''[https://en.wikipedia.org/wiki/Leptin leptin]''' signaling pathways <ref name="Mice">PMID: 20211191</ref>, tumor growth <ref name="cancer">PMID:16887236</ref>, and '''[https://en.wikipedia.org/wiki/Dopamine dopamine]''' regulation <ref name="Schizophrenia">PMID:22596253</ref>.Recently NTSR1 was crystallized bound with the C-terminus of its tridecapeptide '''[https://en.wikipedia.org/wiki/Ligand ligand]''', <scene name='72/721548/Neurotensin/7'>NTS(8-13)</scene>. The shortened ligand was used because it has a higher potency and efficacy than its full-length counterpart<ref name="SONT"/>. Class A GPCRs bind their ligands within the '''[https://en.wikipedia.org/wiki/Transmembrane_protein transmembrane]''' core in a ligand binding pocket. The <scene name='72/721547/Hydrophobic_binding_pocket/5'>ligand binding pocket</scene> in NTSR1 is located at the top of the protein (Figure 1). NTSR1 also contains an '''[https://en.wikipedia.org/wiki/Allosteric_regulation allosteric]''' <scene name='72/721548/Na_bind_pocket/13'>Na⁺ Binding Pocket</scene>. The Na⁺ binding pocket is located directly beneath the ligand binding pocket and the two pockets are separated by the residue Trp321. <ref name="SPGP">PMID:26205105</ref>. NTSR1 has been mutated to exist in both <scene name='72/721548/Ntsr1-elf/6'>active</scene>and <scene name='72/721547/Ntsr1-gw5/8'>active-like</scene> states. This has led to a greater understanding of the structure of NTSR1 and how the structure influences its function.