4u15: Difference between revisions

Latest revision as of 00:49, 28 December 2023

M3-mT4L receptor bound to tiotropium

Structural highlights

4u15 is a 2 chain structure with sequence from Escherichia virus T4 and Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.8Å
Ligands:	0HK, OLC, P6G, TAR
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

D9IEF7_BPT4 ACM3_RAT The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.^[1] ^[2] ^[3]

Publication Abstract from PubMed

G protein-coupled receptors (GPCRs) mediate the majority of cellular responses to hormones and neurotransmitters. Most GPCR crystal structures have been obtained using a fusion protein strategy where the flexible third intracellular loop is replaced by T4 lysozyme (T4L). However, wild-type T4L may not be ideally suited for all GPCRs because of its size and the inherent flexibility between the N- and C-terminal subdomains. Here we report two modified T4L variants, designed to address flexibility and size, that can be used to optimize crystal quality or promote alternative packing interactions. These variants were tested on the M3 muscarinic receptor (M3). The original M3-T4L fusion protein produced twinned crystals that yielded a 3.4 A structure from a 70 crystal data set. We replaced T4L with the modified T4L variants. Both T4L variants yielded M3 muscarinic receptor crystals with alternate lattices that were not twinned, including one that was solved at 2.8 A resolution.

Modified T4 Lysozyme Fusion Proteins Facilitate G Protein-Coupled Receptor Crystallogenesis.,Thorsen TS, Matt R, Weis WI, Kobilka BK Structure. 2014 Oct 23;22(11):1657-1664. doi: 10.1016/j.str.2014.08.022. PMID:25450769^[4]

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

References

↑ Wess J, Maggio R, Palmer JR, Vogel Z. Role of conserved threonine and tyrosine residues in acetylcholine binding and muscarinic receptor activation. A study with m3 muscarinic receptor point mutants. J Biol Chem. 1992 Sep 25;267(27):19313-9. PMID:1527051
↑ Wess J, Gdula D, Brann MR. Site-directed mutagenesis of the m3 muscarinic receptor: identification of a series of threonine and tyrosine residues involved in agonist but not antagonist binding. EMBO J. 1991 Dec;10(12):3729-34. PMID:1657592
↑ Kruse AC, Hu J, Pan AC, Arlow DH, Rosenbaum DM, Rosemond E, Green HF, Liu T, Chae PS, Dror RO, Shaw DE, Weis WI, Wess J, Kobilka BK. Structure and dynamics of the M3 muscarinic acetylcholine receptor. Nature. 2012 Feb 22;482(7386):552-6. doi: 10.1038/nature10867. PMID:22358844 doi:10.1038/nature10867
↑ Thorsen TS, Matt R, Weis WI, Kobilka BK. Modified T4 Lysozyme Fusion Proteins Facilitate G Protein-Coupled Receptor Crystallogenesis. Structure. 2014 Oct 23;22(11):1657-1664. doi: 10.1016/j.str.2014.08.022. PMID:25450769 doi:https://dx.doi.org/10.1016/j.str.2014.08.022

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OCA

[1] Wess J, Maggio R, Palmer JR, Vogel Z. Role of conserved threonine and tyrosine residues in acetylcholine binding and muscarinic receptor activation. A study with m3 muscarinic receptor point mutants. J Biol Chem. 1992 Sep 25;267(27):19313-9. PMID:1527051

[2] Wess J, Gdula D, Brann MR. Site-directed mutagenesis of the m3 muscarinic receptor: identification of a series of threonine and tyrosine residues involved in agonist but not antagonist binding. EMBO J. 1991 Dec;10(12):3729-34. PMID:1657592

[3] Kruse AC, Hu J, Pan AC, Arlow DH, Rosenbaum DM, Rosemond E, Green HF, Liu T, Chae PS, Dror RO, Shaw DE, Weis WI, Wess J, Kobilka BK. Structure and dynamics of the M3 muscarinic acetylcholine receptor. Nature. 2012 Feb 22;482(7386):552-6. doi: 10.1038/nature10867. PMID:22358844 doi:10.1038/nature10867

[4] Thorsen TS, Matt R, Weis WI, Kobilka BK. Modified T4 Lysozyme Fusion Proteins Facilitate G Protein-Coupled Receptor Crystallogenesis. Structure. 2014 Oct 23;22(11):1657-1664. doi: 10.1016/j.str.2014.08.022. PMID:25450769 doi:https://dx.doi.org/10.1016/j.str.2014.08.022

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[2]

[3]

[4]

@@ Line 1: / Line 1: @@
 ==M3-mT4L receptor bound to tiotropium==
-<StructureSection load='4u15' size='340' side='right' caption='[[4u15]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
+<StructureSection load='4u15' size='340' side='right'caption='[[4u15]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4u15]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4U15 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4U15 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4u15]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_virus_T4 Escherichia virus T4] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4U15 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4U15 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0HK:(1R,2R,4S,5S,7S)-7-{[HYDROXY(DITHIOPHEN-2-YL)ACETYL]OXY}-9,9-DIMETHYL-3-OXA-9-AZONIATRICYCLO[3.3.1.0~2,4~]NONANE'>0HK</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=P6G:HEXAETHYLENE+GLYCOL'>P6G</scene>, <scene name='pdbligand=TAR:D(-)-TARTARIC+ACID'>TAR</scene></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]] 2.8&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4u14|4u14]], [[4u16|4u16]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0HK:(1R,2R,4S,5S,7S)-7-{[HYDROXY(DITHIOPHEN-2-YL)ACETYL]OXY}-9,9-DIMETHYL-3-OXA-9-AZONIATRICYCLO[3.3.1.0~2,4~]NONANE'>0HK</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=P6G:HEXAETHYLENE+GLYCOL'>P6G</scene>, <scene name='pdbligand=TAR:D(-)-TARTARIC+ACID'>TAR</scene></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Lysozyme Lysozyme], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.17 3.2.1.17] </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=4u15 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u15 OCA], [https://pdbe.org/4u15 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4u15 RCSB], [https://www.ebi.ac.uk/pdbsum/4u15 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4u15 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=4u15 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u15 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4u15 RCSB], [http://www.ebi.ac.uk/pdbsum/4u15 PDBsum]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/ACM3_RAT ACM3_RAT]] The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.<ref>PMID:1527051</ref> <ref>PMID:1657592</ref> <ref>PMID:22358844</ref>
+[https://www.uniprot.org/uniprot/D9IEF7_BPT4 D9IEF7_BPT4] [https://www.uniprot.org/uniprot/ACM3_RAT ACM3_RAT] The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.<ref>PMID:1527051</ref> <ref>PMID:1657592</ref> <ref>PMID:22358844</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 18: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4u15" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Muscarinic acetylcholine receptor|Muscarinic acetylcholine receptor]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Lysozyme]]
+[[Category: Escherichia virus T4]]
-[[Category: Kobilka, B]]
+[[Category: Large Structures]]
-[[Category: Matt, R]]
+[[Category: Rattus norvegicus]]
-[[Category: Thorsen, T S]]
+[[Category: Kobilka B]]
-[[Category: Weis, W I]]
+[[Category: Matt R]]
-[[Category: Gpcr t4l stabillized crystallography]]
+[[Category: Thorsen TS]]
-[[Category: Membrane protein]]
+[[Category: Weis WI]]
-[[Category: Membrane protein-inhibitor complex]]

4u15: Difference between revisions

Latest revision as of 00:49, 28 December 2023

M3-mT4L receptor bound to tiotropium

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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