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==== | ==Structure of human beta1 adrenergic receptor bound to norepinephrine and nanobody 6B9== | ||
<StructureSection load='7bu6' size='340' side='right'caption='[[7bu6]]' scene=''> | <StructureSection load='7bu6' size='340' side='right'caption='[[7bu6]], [[Resolution|resolution]] 2.70Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | <table><tr><td colspan='2'>[[7bu6]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Camelidae_mixed_library Camelidae mixed library], [https://en.wikipedia.org/wiki/Escherichia_virus_T4 Escherichia virus T4] 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=7BU6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BU6 FirstGlance]. <br> | ||
</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=7bu6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bu6 OCA], [https://pdbe.org/7bu6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bu6 RCSB], [https://www.ebi.ac.uk/pdbsum/7bu6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bu6 ProSAT]</span></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=480:(2S)-2,3-DIHYDROXYPROPYL+OCTANOATE'>480</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=E5E:[(2~{R})-2-[3,4-bis(oxidanyl)phenyl]-2-oxidanyl-ethyl]azanium'>E5E</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PRD_900001:alpha-maltose'>PRD_900001</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=7bu6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bu6 OCA], [https://pdbe.org/7bu6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bu6 RCSB], [https://www.ebi.ac.uk/pdbsum/7bu6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bu6 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/D9IEF7_BPT4 D9IEF7_BPT4] [https://www.uniprot.org/uniprot/ADRB1_HUMAN ADRB1_HUMAN] Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately equal affinity. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Beta adrenergic receptors (betaARs) mediate physiologic responses to the catecholamines epinephrine and norepinephrine released by the sympathetic nervous system. While the hormone epinephrine binds beta1AR and beta2AR with similar affinity, the smaller neurotransmitter norepinephrine is approximately tenfold selective for the beta1AR. To understand the structural basis for this physiologically important selectivity, we solved the crystal structures of the human beta1AR bound to an antagonist carazolol and different agonists including norepinephrine, epinephrine and BI-167107. Structural comparison revealed that the catecholamine-binding pockets are identical between beta1AR and beta2AR, but the extracellular vestibules have different shapes and electrostatic properties. Metadynamics simulations and mutagenesis studies revealed that these differences influence the path norepinephrine takes to the orthosteric pocket and contribute to the different association rates and thus different affinities. | |||
Binding pathway determines norepinephrine selectivity for the human beta1AR over beta2AR.,Xu X, Kaindl J, Clark MJ, Hubner H, Hirata K, Sunahara RK, Gmeiner P, Kobilka BK, Liu X Cell Res. 2020 Oct 22. pii: 10.1038/s41422-020-00424-2. doi:, 10.1038/s41422-020-00424-2. PMID:33093660<ref>PMID:33093660</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7bu6" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Adrenergic receptor 3D structures|Adrenergic receptor 3D structures]] | |||
*[[Antibody 3D structures|Antibody 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Camelidae mixed library]] | |||
[[Category: Escherichia virus T4]] | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Clark M]] | ||
[[Category: Gmeiner P]] | |||
[[Category: Hirata K]] | |||
[[Category: Hubner H]] | |||
[[Category: Kaindl J]] | |||
[[Category: Kobilka BK]] | |||
[[Category: Liu X]] | |||
[[Category: Sunahara R]] | |||
[[Category: Xu X]] | |||
Latest revision as of 13:53, 23 October 2024
Structure of human beta1 adrenergic receptor bound to norepinephrine and nanobody 6B9Structure of human beta1 adrenergic receptor bound to norepinephrine and nanobody 6B9
Structural highlights
FunctionD9IEF7_BPT4 ADRB1_HUMAN Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately equal affinity. Publication Abstract from PubMedBeta adrenergic receptors (betaARs) mediate physiologic responses to the catecholamines epinephrine and norepinephrine released by the sympathetic nervous system. While the hormone epinephrine binds beta1AR and beta2AR with similar affinity, the smaller neurotransmitter norepinephrine is approximately tenfold selective for the beta1AR. To understand the structural basis for this physiologically important selectivity, we solved the crystal structures of the human beta1AR bound to an antagonist carazolol and different agonists including norepinephrine, epinephrine and BI-167107. Structural comparison revealed that the catecholamine-binding pockets are identical between beta1AR and beta2AR, but the extracellular vestibules have different shapes and electrostatic properties. Metadynamics simulations and mutagenesis studies revealed that these differences influence the path norepinephrine takes to the orthosteric pocket and contribute to the different association rates and thus different affinities. Binding pathway determines norepinephrine selectivity for the human beta1AR over beta2AR.,Xu X, Kaindl J, Clark MJ, Hubner H, Hirata K, Sunahara RK, Gmeiner P, Kobilka BK, Liu X Cell Res. 2020 Oct 22. pii: 10.1038/s41422-020-00424-2. doi:, 10.1038/s41422-020-00424-2. PMID:33093660[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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