3d4s: Difference between revisions
No edit summary |
No edit summary |
||
| (15 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
< | ==Cholesterol bound form of human beta2 adrenergic receptor.== | ||
<StructureSection load='3d4s' size='340' side='right'caption='[[3d4s]], [[Resolution|resolution]] 2.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3d4s]] is a 1 chain structure with sequence from [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=3D4S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3D4S FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8Å</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=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=TIM:(2S)-1-(TERT-BUTYLAMINO)-3-[(4-MORPHOLIN-4-YL-1,2,5-THIADIAZOL-3-YL)OXY]PROPAN-2-OL'>TIM</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=3d4s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3d4s OCA], [https://pdbe.org/3d4s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3d4s RCSB], [https://www.ebi.ac.uk/pdbsum/3d4s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3d4s ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/ADRB2_HUMAN ADRB2_HUMAN] Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately 30-fold greater affinity than it does norepinephrine.[https://www.uniprot.org/uniprot/ENLYS_BPT4 ENLYS_BPT4] 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.<ref>PMID:22389108</ref> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/d4/3d4s_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3d4s ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The role of cholesterol in eukaryotic membrane protein function has been attributed primarily to an influence on membrane fluidity and curvature. We present the 2.8 A resolution crystal structure of a thermally stabilized human beta(2)-adrenergic receptor bound to cholesterol and the partial inverse agonist timolol. The receptors pack as monomers in an antiparallel association with two distinct cholesterol molecules bound per receptor, but not in the packing interface, thereby indicating a structurally relevant cholesterol-binding site between helices I, II, III, and IV. Thermal stability analysis using isothermal denaturation confirms that a cholesterol analog significantly enhances the stability of the receptor. A consensus motif is defined that predicts cholesterol binding for 44% of human class A receptors, suggesting that specific sterol binding is important to the structure and stability of other G protein-coupled receptors, and that this site may provide a target for therapeutic discovery. | |||
A specific cholesterol binding site is established by the 2.8 A structure of the human beta2-adrenergic receptor.,Hanson MA, Cherezov V, Griffith MT, Roth CB, Jaakola VP, Chien EY, Velasquez J, Kuhn P, Stevens RC Structure. 2008 Jun;16(6):897-905. PMID:18547522<ref>PMID:18547522</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3d4s" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
*[[Adrenergic receptor 3D structures|Adrenergic receptor 3D structures]] | |||
[[Category: Homo sapiens | *[[Lysozyme 3D structures|Lysozyme 3D structures]] | ||
[[Category: | == References == | ||
[[Category: Cherezov | <references/> | ||
[[Category: Chien | __TOC__ | ||
[[Category: Griffith | </StructureSection> | ||
[[Category: Hanson | [[Category: Escherichia virus T4]] | ||
[[Category: Jaakola | [[Category: Homo sapiens]] | ||
[[Category: Kuhn | [[Category: Large Structures]] | ||
[[Category: Roth | [[Category: Cherezov V]] | ||
[[Category: Stevens | [[Category: Chien EYT]] | ||
[[Category: Velasquez | [[Category: Griffith MT]] | ||
[[Category: Hanson MA]] | |||
[[Category: Jaakola V-P]] | |||
[[Category: Kuhn P]] | |||
[[Category: Roth CB]] | |||
[[Category: Stevens RC]] | |||
[[Category: Velasquez J]] | |||
Latest revision as of 11:57, 30 October 2024
Cholesterol bound form of human beta2 adrenergic receptor.Cholesterol bound form of human beta2 adrenergic receptor.
Structural highlights
FunctionADRB2_HUMAN Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately 30-fold greater affinity than it does norepinephrine.ENLYS_BPT4 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.[1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe role of cholesterol in eukaryotic membrane protein function has been attributed primarily to an influence on membrane fluidity and curvature. We present the 2.8 A resolution crystal structure of a thermally stabilized human beta(2)-adrenergic receptor bound to cholesterol and the partial inverse agonist timolol. The receptors pack as monomers in an antiparallel association with two distinct cholesterol molecules bound per receptor, but not in the packing interface, thereby indicating a structurally relevant cholesterol-binding site between helices I, II, III, and IV. Thermal stability analysis using isothermal denaturation confirms that a cholesterol analog significantly enhances the stability of the receptor. A consensus motif is defined that predicts cholesterol binding for 44% of human class A receptors, suggesting that specific sterol binding is important to the structure and stability of other G protein-coupled receptors, and that this site may provide a target for therapeutic discovery. A specific cholesterol binding site is established by the 2.8 A structure of the human beta2-adrenergic receptor.,Hanson MA, Cherezov V, Griffith MT, Roth CB, Jaakola VP, Chien EY, Velasquez J, Kuhn P, Stevens RC Structure. 2008 Jun;16(6):897-905. PMID:18547522[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||