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6pb0

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Cryo-EM structure of Urocortin 1-bound Corticotropin-releasing factor 1 receptor in complex with Gs protein and Nb35

6pb0, resolution 3.00Å

Structural highlights

6pb0 is a 6 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3Å
Ligands:
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CRFR1_HUMAN Receptor for corticotropin releasing factor (CRH). Shows high-affinity CRF binding. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.^[1]

Publication Abstract from PubMed

Corticotropin-releasing factor (CRF) and the three related peptides urocortins 1-3 (UCN1-UCN3) are endocrine hormones that control the stress responses by activating CRF1R and CRF2R, two members of class B G-protein-coupled receptors (GPCRs). Here, we present two cryoelectron microscopy (cryo-EM) structures of UCN1-bound CRF1R and CRF2R with the stimulatory G protein. In both structures, UCN1 adopts a single straight helix with its N terminus dipped into the receptor transmembrane bundle. Although the peptide-binding residues in CRF1R and CRF2R are different from other members of class B GPCRs, the residues involved in receptor activation and G protein coupling are conserved. In addition, both structures reveal bound cholesterol molecules to the receptor transmembrane helices. Our structures define the basis of ligand-binding specificity in the CRF receptor-hormone system, establish a common mechanism of class B GPCR activation and G protein coupling, and provide a paradigm for studying membrane protein-lipid interactions for class B GPCRs.

Molecular Basis for Hormone Recognition and Activation of Corticotropin-Releasing Factor Receptors.,Ma S, Shen Q, Zhao LH, Mao C, Zhou XE, Shen DD, de Waal PW, Bi P, Li C, Jiang Y, Wang MW, Sexton PM, Wootten D, Melcher K, Zhang Y, Xu HE Mol Cell. 2020 Feb 6;77(3):669-680.e4. doi: 10.1016/j.molcel.2020.01.013. Epub, 2020 Jan 30. PMID:32004470^[2]

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

References

↑ Pioszak AA, Parker NR, Suino-Powell K, Xu HE. Molecular recognition of corticotropin-releasing factor by its G-protein-coupled receptor CRFR1. J Biol Chem. 2008 Nov 21;283(47):32900-12. Epub 2008 Sep 17. PMID:18801728 doi:10.1074/jbc.M805749200
↑ Ma S, Shen Q, Zhao LH, Mao C, Zhou XE, Shen DD, de Waal PW, Bi P, Li C, Jiang Y, Wang MW, Sexton PM, Wootten D, Melcher K, Zhang Y, Xu HE. Molecular Basis for Hormone Recognition and Activation of Corticotropin-Releasing Factor Receptors. Mol Cell. 2020 Feb 6;77(3):669-680.e4. doi: 10.1016/j.molcel.2020.01.013. Epub, 2020 Jan 30. PMID:32004470 doi:http://dx.doi.org/10.1016/j.molcel.2020.01.013

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/6pb0"

@@ Line 3: / Line 3: @@
 <SX load='6pb0' size='340' side='right' viewer='molstar' caption='[[6pb0]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6pb0]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Synthetic_construct_sequences Synthetic construct sequences]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PB0 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6PB0 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6pb0]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PB0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6PB0 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CRHR1, CRFR, CRFR1, CRHR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), UCN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), GNAS, GNAS1, GSP ([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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</scene></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=6pb0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pb0 OCA], [http://pdbe.org/6pb0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6pb0 RCSB], [http://www.ebi.ac.uk/pdbsum/6pb0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6pb0 ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6pb0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pb0 OCA], [https://pdbe.org/6pb0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6pb0 RCSB], [https://www.ebi.ac.uk/pdbsum/6pb0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6pb0 ProSAT]</span></td></tr>
 </table>
-== Disease ==
-[[http://www.uniprot.org/uniprot/GNAS2_HUMAN GNAS2_HUMAN]] Pseudopseudohypoparathyroidism;Pseudohypoparathyroidism type 1A;Progressive osseous heteroplasia;Polyostotic fibrous dysplasia;Monostotic fibrous dysplasia;Pseudohypoparathyroidism type 1C;Pseudohypoparathyroidism type 1B;McCune-Albright syndrome. The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry. Most affected individuals have defects in methylation of the gene. In some cases microdeletions involving the STX16 appear to cause loss of methylation at exon A/B of GNAS, resulting in PHP1B. Paternal uniparental isodisomy have also been observed.  The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.
 == Function ==
-[[http://www.uniprot.org/uniprot/GNAS2_HUMAN GNAS2_HUMAN]] Guanine nucleotide-binding proteins (G proteins) function as transducers in numerous signaling pathways controlled by G protein-coupled receptors (GPCRs) (PubMed:17110384). Signaling involves the activation of adenylyl cyclases, resulting in increased levels of the signaling molecule cAMP (PubMed:26206488, PubMed:8702665). GNAS functions downstream of several GPCRs, including beta-adrenergic receptors (PubMed:21488135). Stimulates the Ras signaling pathway via RAPGEF2 (PubMed:12391161).<ref>PMID:12391161</ref> <ref>PMID:17110384</ref> <ref>PMID:21488135</ref> <ref>PMID:26206488</ref> <ref>PMID:8702665</ref>  [[http://www.uniprot.org/uniprot/UCN1_HUMAN UCN1_HUMAN]] Acts in vitro to stimulate the secretion of adrenocorticotropic hormone (ACTH). Binds with high affinity to CRF receptor types 1, 2-alpha, and 2-beta. [[http://www.uniprot.org/uniprot/CRFR1_HUMAN CRFR1_HUMAN]] Receptor for corticotropin releasing factor (CRH). Shows high-affinity CRF binding. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.<ref>PMID:18801728</ref>  [[http://www.uniprot.org/uniprot/GBB1_HUMAN 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.<ref>PMID:18611381</ref>  [[http://www.uniprot.org/uniprot/GBG2_HUMAN 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).
+[https://www.uniprot.org/uniprot/CRFR1_HUMAN CRFR1_HUMAN] Receptor for corticotropin releasing factor (CRH). Shows high-affinity CRF binding. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.<ref>PMID:18801728</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 23: / Line 21: @@
 ==See Also==
+*[[GTP-binding protein 3D structures|GTP-binding protein 3D structures]]
 *[[Transducin 3D structures|Transducin 3D structures]]
 == References ==
@@ Line 28: / Line 27: @@
 __TOC__
 </SX>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Synthetic construct sequences]]
+[[Category: Synthetic construct]]
-[[Category: Bi, P]]
+[[Category: Bi P]]
-[[Category: Jiang, Y]]
+[[Category: Jiang Y]]
-[[Category: Li, C]]
+[[Category: Li C]]
-[[Category: Ma, S]]
+[[Category: Ma S]]
-[[Category: Mao, C]]
+[[Category: Mao C]]
-[[Category: Melcher, K]]
+[[Category: Melcher K]]
-[[Category: Sexton, P M]]
+[[Category: Sexton PM]]
-[[Category: Shen, D D]]
+[[Category: Shen D-D]]
-[[Category: Shen, Q]]
+[[Category: Shen Q]]
-[[Category: Waal, P W.de]]
+[[Category: Wang M-W]]
-[[Category: Wang, M W]]
+[[Category: Wootten D]]
-[[Category: Wootten, D]]
+[[Category: Xu HE]]
-[[Category: Xu, H E]]
+[[Category: Zhang Y]]
-[[Category: Zhang, Y]]
+[[Category: Zhao L-H]]
-[[Category: Zhao, L H]]
+[[Category: Zhou XE]]
-[[Category: Zhou, X E]]
+[[Category: De Waal PW]]
-[[Category: Corticotropin-releasing factor 1 receptor]]
-[[Category: Gpcr]]
-[[Category: Gs protein]]
-[[Category: Signaling protein]]
-[[Category: Urocortins1]]

6pb0

From Proteopedia

Current revision

Cryo-EM structure of Urocortin 1-bound Corticotropin-releasing factor 1 receptor in complex with Gs protein and Nb35

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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