6pfo
From Proteopedia
(Difference between revisions)
| Line 3: | Line 3: | ||
<StructureSection load='6pfo' size='340' side='right'caption='[[6pfo]], [[Resolution|resolution]] 1.78Å' scene=''> | <StructureSection load='6pfo' size='340' side='right'caption='[[6pfo]], [[Resolution|resolution]] 1.78Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6pfo]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PFO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6PFO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6pfo]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PFO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6PFO FirstGlance]. <br> |
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MAL:MALTOSE'>MAL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MAL:MALTOSE'>MAL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | ||
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr> | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CALCR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</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=6pfo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pfo OCA], [http://pdbe.org/6pfo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6pfo RCSB], [http://www.ebi.ac.uk/pdbsum/6pfo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6pfo ProSAT]</span></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=6pfo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pfo OCA], [http://pdbe.org/6pfo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6pfo RCSB], [http://www.ebi.ac.uk/pdbsum/6pfo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6pfo ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The class B G protein-coupled receptor (GPCR) calcitonin receptor (CTR) is a drug target for osteoporosis and diabetes. N-glycosylation of asparagine 130 in its extracellular domain (ECD) enhances calcitonin hormone affinity with the proximal GlcNAc residue mediating this effect through an unknown mechanism. Here, we present two crystal structures of salmon calcitonin-bound, GlcNAc-bearing CTR ECD at 1.78 and 2.85 A resolutions and analyze the mechanism of the glycan effect. The N130 GlcNAc does not contact the hormone. Surprisingly, the structures are nearly identical to a structure of hormone-bound, N-glycan-free ECD, which suggested that the GlcNAc might affect CTR dynamics not observed in the static crystallographic snapshots. Hydrogen-deuterium exchange mass spectrometry and molecular dynamics simulations revealed that glycosylation stabilized a beta-sheet adjacent to the N130 GlcNAc and the N-terminal alpha-helix near the peptide-binding site, while increasing flexibility of the peptide-binding site turret loop. These changes due to N-glycosylation increased the ligand on-rate and decreased its off rate. The glycan effect extended to RAMP-CTR amylin receptor complexes and was also conserved in the related CGRP receptor. These results reveal that N-glycosylation can modulate GPCR function by altering receptor dynamics. | ||
| + | |||
| + | Calcitonin receptor N-glycosylation enhances peptide hormone affinity by controlling receptor dynamics.,Lee SM, Jeong Y, Simms J, Warner ML, Poyner DR, Chung KY, Pioszak AA J Mol Biol. 2020 Feb 6. pii: S0022-2836(20)30092-9. doi:, 10.1016/j.jmb.2020.01.028. PMID:32035902<ref>PMID:32035902</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6pfo" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Bacillus coli migula 1895]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Lee, S]] | [[Category: Lee, S]] | ||
Revision as of 07:27, 19 February 2020
Crystal structure of N-glycosylated human calcitonin receptor extracellular domain in complex with salmon calcitonin (16-32)
| |||||||||||
