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3c4m

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[[Image:3c4m.png|left|200px]]
 
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{{STRUCTURE_3c4m| PDB=3c4m | SCENE= }}
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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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<StructureSection load='3c4m' size='340' side='right'caption='[[3c4m]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
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== Structural highlights ==
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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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</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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<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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{{ABSTRACT_PUBMED_18375760}}
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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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==About this Structure==
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<div class="pdbe-citations 3c4m" style="background-color:#fffaf0;"></div>
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[[3c4m]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3C4M OCA].
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== References ==
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<references/>
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==Reference==
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__TOC__
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<ref group="xtra">PMID:018375760</ref><references group="xtra"/>
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</StructureSection>
[[Category: Escherichia coli]]
[[Category: Escherichia coli]]
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[[Category: Pioszak, A A.]]
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[[Category: Homo sapiens]]
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[[Category: Xu, H E.]]
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[[Category: Large Structures]]
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[[Category: Cleavage on pair of basic residue]]
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[[Category: Pioszak AA]]
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[[Category: Disease mutation]]
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[[Category: Xu HE]]
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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: Receptor]]
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[[Category: Secreted]]
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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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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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