4z9g
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==Crystal structure of human corticotropin-releasing factor receptor 1 (CRF1R) in complex with the antagonist CP-376395 in a hexagonal setting with translational non-crystallographic symmetry== | ==Crystal structure of human corticotropin-releasing factor receptor 1 (CRF1R) in complex with the antagonist CP-376395 in a hexagonal setting with translational non-crystallographic symmetry== | ||
| - | <StructureSection load='4z9g' size='340' side='right' caption='[[4z9g]], [[Resolution|resolution]] 3.18Å' scene=''> | + | <StructureSection load='4z9g' size='340' side='right'caption='[[4z9g]], [[Resolution|resolution]] 3.18Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[4z9g]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Z9G OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[4z9g]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Enterobacteria_phage_RB51 Enterobacteria phage RB51] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Z9G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Z9G FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1Q5:3,6-DIMETHYL-N-(PENTAN-3-YL)-2-(2,4,6-TRIMETHYLPHENOXY)PYRIDIN-4-AMINE'>1Q5</scene>, <scene name='pdbligand=OLA:OLEIC+ACID'>OLA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.183Å</td></tr> |
| - | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1Q5:3,6-DIMETHYL-N-(PENTAN-3-YL)-2-(2,4,6-TRIMETHYLPHENOXY)PYRIDIN-4-AMINE'>1Q5</scene>, <scene name='pdbligand=OLA:OLEIC+ACID'>OLA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=4z9g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4z9g OCA], [https://pdbe.org/4z9g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4z9g RCSB], [https://www.ebi.ac.uk/pdbsum/4z9g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4z9g ProSAT]</span></td></tr> | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | |
</table> | </table> | ||
== Function == | == Function == | ||
| - | [ | + | [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> [https://www.uniprot.org/uniprot/C3V2B5_BPR51 C3V2B5_BPR51] Endolysin with lysozyme activity that degrades host peptidoglycans and participates with the holin and spanin proteins in the sequential events which lead to the programmed host cell lysis releasing the mature viral particles. Once the holin has permeabilized the host cell membrane, the endolysin can reach the periplasm and break down the peptidoglycan layer.[HAMAP-Rule:MF_04110] |
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The structural analysis of class B G protein-coupled receptors (GPCR), cell surface proteins responding to peptide hormones, has until recently been restricted to the extracellular domain (ECD). Corticotropin-releasing factor receptor type 1 (CRF1R) is a class B receptor mediating stress response and also considered a drug target for depression and anxiety. Here we report the crystal structure of the transmembrane domain of human CRF1R in complex with the small-molecule antagonist CP-376395 in a hexagonal setting with translational non-crystallographic symmetry. Molecular dynamics and metadynamics simulations on this novel structure and the existing TMD structure for CRF1R provides insight as to how the small molecule ligand gains access to the induced-fit allosteric binding site with implications for the observed selectivity against CRF2R. Furthermore, molecular dynamics simulations performed using a full-length receptor model point to key interactions between the ECD and extracellular loop 3 of the TMD providing insight into the full inactive state of multidomain class B GPCRs. | ||
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| + | Decoding Corticotropin-Releasing Factor Receptor Type 1 Crystal Structures.,Dore AS, Bortolato A, Hollenstein K, Cheng RKY, Read RJ, Marshall FH Curr Mol Pharmacol. 2017;10(4):334-344. doi: 10.2174/1874467210666170110114727. PMID:28183242<ref>PMID:28183242</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 4z9g" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Enterobacteria phage RB51]] |
| - | [[Category: | + | [[Category: Homo sapiens]] |
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Bortolato A]] |
| - | [[Category: | + | [[Category: Cheng RKY]] |
| - | [[Category: | + | [[Category: Dore AS]] |
| - | [[Category: | + | [[Category: Hollenstein K]] |
| - | [[Category: | + | [[Category: Marshall FH]] |
| - | [[Category: | + | [[Category: Read RJ]] |
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Current revision
Crystal structure of human corticotropin-releasing factor receptor 1 (CRF1R) in complex with the antagonist CP-376395 in a hexagonal setting with translational non-crystallographic symmetry
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