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6os9

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human Neurotensin Receptor 1 (hNTSR1) - Gi1 Protein Complex in canonical conformation (C state)

6os9, resolution 3.00Å

Structural highlights

6os9 is a 6 chain structure with sequence from Human and Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	NTSR1, NTRR (HUMAN), GNAI1 (HUMAN), GNB1 (HUMAN), GNG2 (HUMAN)
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[GBB1_HUMAN] Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction.^[1] [NTR1_HUMAN] Receptor for the tridecapeptide neurotensin. It is associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. [GNAI1_HUMAN] Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(i) proteins are involved in hormonal regulation of adenylate cyclase: they inhibit the cyclase in response to beta-adrenergic stimuli. The inactive GDP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. May play a role in cell division.^[2] ^[3] [GBG2_HUMAN] Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction (By similarity).

Publication Abstract from PubMed

Neurotensin receptor 1 (NTSR1) is a G-protein-coupled receptor (GPCR) that engages multiple subtypes of G protein, and is involved in the regulation of blood pressure, body temperature, weight and the response to pain. Here we present structures of human NTSR1 in complex with the agonist JMV449 and the heterotrimeric Gi1 protein, at a resolution of 3 A. We identify two conformations: a canonical-state complex that is similar to recently reported GPCR-Gi/o complexes (in which the nucleotide-binding pocket adopts more flexible conformations that may facilitate nucleotide exchange), and a non-canonical state in which the G protein is rotated by about 45 degrees relative to the receptor and exhibits a more rigid nucleotide-binding pocket. In the non-canonical state, NTSR1 exhibits features of both active and inactive conformations, which suggests that the structure may represent an intermediate form along the activation pathway of G proteins. This structural information, complemented by molecular dynamics simulations and functional studies, provides insights into the complex process of G-protein activation.

Conformational transitions of a neurotensin receptor 1-Gi1 complex.,Kato HE, Zhang Y, Hu H, Suomivuori CM, Kadji FMN, Aoki J, Krishna Kumar K, Fonseca R, Hilger D, Huang W, Latorraca NR, Inoue A, Dror RO, Kobilka BK, Skiniotis G Nature. 2019 Jun 26. pii: 10.1038/s41586-019-1337-6. doi:, 10.1038/s41586-019-1337-6. PMID:31243364^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Johnston CA, Kimple AJ, Giguere PM, Siderovski DP. Structure of the parathyroid hormone receptor C terminus bound to the G-protein dimer Gbeta1gamma2. Structure. 2008 Jul;16(7):1086-94. PMID:18611381 doi:http://dx.doi.org/10.1016/j.str.2008.04.010
↑ Cho H, Kehrl JH. Localization of Gi alpha proteins in the centrosomes and at the midbody: implication for their role in cell division. J Cell Biol. 2007 Jul 16;178(2):245-55. PMID:17635935 doi:10.1083/jcb.200604114
↑ Johnston CA, Siderovski DP. Structural basis for nucleotide exchange on G alpha i subunits and receptor coupling specificity. Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):2001-6. Epub 2007 Jan 30. PMID:17264214
↑ Kato HE, Zhang Y, Hu H, Suomivuori CM, Kadji FMN, Aoki J, Krishna Kumar K, Fonseca R, Hilger D, Huang W, Latorraca NR, Inoue A, Dror RO, Kobilka BK, Skiniotis G. Conformational transitions of a neurotensin receptor 1-Gi1 complex. Nature. 2019 Jun 26. pii: 10.1038/s41586-019-1337-6. doi:, 10.1038/s41586-019-1337-6. PMID:31243364 doi:http://dx.doi.org/10.1038/s41586-019-1337-6

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6os9"

@@ Line 3: / Line 3: @@
 <SX load='6os9' size='340' side='right' viewer='molstar' caption='[[6os9]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6os9]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OS9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6OS9 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6os9]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OS9 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6OS9 FirstGlance]. <br>
 </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NTSR1, NTRR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), GNAI1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), GNB1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), GNG2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6os9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6os9 OCA], [http://pdbe.org/6os9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6os9 RCSB], [http://www.ebi.ac.uk/pdbsum/6os9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6os9 ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6os9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6os9 OCA], [http://pdbe.org/6os9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6os9 RCSB], [http://www.ebi.ac.uk/pdbsum/6os9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6os9 ProSAT]</span></td></tr>
 </table>
 == Function ==

6os9

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Current revision

human Neurotensin Receptor 1 (hNTSR1) - Gi1 Protein Complex in canonical conformation (C state)

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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