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3c4m

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{{Seed}}
 
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[[Image:3c4m.png|left|200px]]
 
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==Structure of human parathyroid hormone in complex with the extracellular domain of its G-protein-coupled receptor (PTH1R)==
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The line below this paragraph, containing "STRUCTURE_3c4m", creates the "Structure Box" on the page.
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<StructureSection load='3c4m' size='340' side='right'caption='[[3c4m]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[3c4m]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] 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=3C4M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3C4M FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.95&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=PRD_900001:alpha-maltose'>PRD_900001</scene></td></tr>
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{{STRUCTURE_3c4m| PDB=3c4m | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3c4m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3c4m OCA], [https://pdbe.org/3c4m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3c4m RCSB], [https://www.ebi.ac.uk/pdbsum/3c4m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3c4m ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/PTH1R_HUMAN PTH1R_HUMAN] Blomstrand lethal chondrodysplasia;Dental ankylosis;Eiken syndrome;Metaphyseal chondrodysplasia, Jansen type;Enchondromatosis. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease may be caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.
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== Function ==
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[https://www.uniprot.org/uniprot/MALE_ECOLI MALE_ECOLI] Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides.[https://www.uniprot.org/uniprot/PTH1R_HUMAN PTH1R_HUMAN] This is a receptor for parathyroid hormone and for parathyroid hormone-related peptide. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase and also a phosphatidylinositol-calcium second messenger system.<ref>PMID:18611381</ref> <ref>PMID:20172855</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/c4/3c4m_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=3c4m ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Parathyroid hormone (PTH) is central to calcium homeostasis and bone maintenance in vertebrates, and as such it has been used for treating osteoporosis. It acts primarily by binding to its receptor, PTH1R, a member of the class B G protein-coupled receptor (GPCR) family that also includes receptors for glucagon, calcitonin, and other therapeutically important peptide hormones. Despite considerable interest and much research, determining the structure of the receptor-hormone complex has been hindered by difficulties in purifying the receptor and obtaining diffraction-quality crystals. Here, we present a method for expression and purification of the extracellular domain (ECD) of human PTH1R engineered as a maltose-binding protein (MBP) fusion that readily crystallizes. The 1.95-A structure of PTH bound to the MBP-PTH1R-ECD fusion reveals that PTH docks as an amphipathic helix into a central hydrophobic groove formed by a three-layer alpha-beta-betaalpha fold of the PTH1R ECD, resembling a hot dog in a bun. Conservation in the ECD scaffold and the helical structure of peptide hormones emphasizes this hot dog model as a general mechanism of hormone recognition common to class B GPCRs. Our findings reveal critical insights into PTH actions and provide a rational template for drug design that targets this hormone signaling pathway.
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===Structure of human parathyroid hormone in complex with the extracellular domain of its G-protein-coupled receptor (PTH1R)===
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Molecular recognition of parathyroid hormone by its G protein-coupled receptor.,Pioszak AA, Xu HE Proc Natl Acad Sci U S A. 2008 Apr 1;105(13):5034-9. Epub 2008 Mar 28. PMID:18375760<ref>PMID:18375760</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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The line below this paragraph, {{ABSTRACT_PUBMED_18375760}}, adds the Publication Abstract to the page
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<div class="pdbe-citations 3c4m" style="background-color:#fffaf0;"></div>
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(as it appears on PubMed at http://www.pubmed.gov), where 18375760 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_18375760}}
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__TOC__
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</StructureSection>
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==About this Structure==
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[[Category: Escherichia coli]]
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3C4M is a 4 chains structure of sequences from [http://en.wikipedia.org/wiki/Escherichia_coli,_homo_sapiens Escherichia coli, homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3C4M OCA].
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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==Reference==
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[[Category: Pioszak AA]]
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<ref group="xtra">PMID:18375760</ref><references group="xtra"/>
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[[Category: Xu HE]]
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[[Category: Escherichia coli, homo sapiens]]
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[[Category: Pioszak, A A.]]
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[[Category: Xu, H E.]]
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[[Category: Cleavage on pair of basic residue]]
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[[Category: Disease mutation]]
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[[Category: Dwarfism]]
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[[Category: G-protein-coupled receptor]]
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[[Category: Glycoprotein]]
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[[Category: Membrane]]
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[[Category: Membrane protein]]
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[[Category: Parathyroid hormone]]
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[[Category: Periplasm]]
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[[Category: Receptor]]
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[[Category: Secreted]]
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[[Category: Signal]]
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[[Category: Sugar transport]]
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[[Category: Transducer]]
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[[Category: Transmembrane]]
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[[Category: Transport]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 18 03:40:44 2009''
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Current revision

Structure of human parathyroid hormone in complex with the extracellular domain of its G-protein-coupled receptor (PTH1R)

PDB ID 3c4m

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