1hyk
From Proteopedia
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==AGOUTI-RELATED PROTEIN (87-132) (AC-AGRP(87-132))== | ==AGOUTI-RELATED PROTEIN (87-132) (AC-AGRP(87-132))== | ||
| - | <StructureSection load='1hyk' size='340' side='right'caption='[[1hyk | + | <StructureSection load='1hyk' size='340' side='right'caption='[[1hyk]]' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[1hyk]] is a 1 chain structure. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1qu8 1qu8]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HYK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HYK FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1hyk]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1qu8 1qu8]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HYK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HYK FirstGlance]. <br> |
| - | </td></tr><tr id=' | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=1hyk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hyk OCA], [https://pdbe.org/1hyk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1hyk RCSB], [https://www.ebi.ac.uk/pdbsum/1hyk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1hyk ProSAT]</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=1hyk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hyk OCA], [https://pdbe.org/1hyk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1hyk RCSB], [https://www.ebi.ac.uk/pdbsum/1hyk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1hyk ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
| - | + | [https://www.uniprot.org/uniprot/AGRP_HUMAN AGRP_HUMAN] Genetic variations in AGRP may be a cause of obesity (OBESITY) [MIM:[https://omim.org/entry/601665 601665]. It is a condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat.<ref>PMID:12213871</ref> | |
== Function == | == Function == | ||
| - | + | [https://www.uniprot.org/uniprot/AGRP_HUMAN AGRP_HUMAN] Plays a role in weight homeostasis. Involved in the control of feeding behavior through the central melanocortin system. Acts as alpha melanocyte-stimulating hormone antagonist by inhibiting cAMP production mediated by stimulation of melanocortin receptors within the hypothalamus and adrenal gland. Has very low activity with MC5R (By similarity). Is an inverse agonist for MC3R and MC4R being able to suppress their constitutive activity. It promotes MC3R and MC4R endocytosis in an arrestin-dependent manner.<ref>PMID:9892020</ref> <ref>PMID:11145747</ref> <ref>PMID:17041250</ref> <ref>PMID:10371151</ref> <ref>PMID:15927146</ref> | |
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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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=1hyk ConSurf]. | </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=1hyk ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | The structure of the chemically synthesized C-terminal region of the human agouti related protein (AGRP) was determined by 2D 1H NMR. Referred to as minimized agouti related protein, MARP is a 46 residue polypeptide containing 10 Cys residues involved in five disulfide bonds that retains the biological activity of full length AGRP. AGRP is a mammalian signaling molecule, involved in weight homeostasis, that causes adult onset obesity when overexpressed in mice. AGRP was originally identified by homology to the agouti protein, another potent signaling molecule involved in obesity disorders in mice. While AGRP's exact mechanism of action is unknown, it has been identified as a competitive antagonist of melanocortin receptors 3 and 4 (MC3r, MC4r), and MC4r in particular is implicated in the hypothalamic control of feeding behavior. Full length agouti and AGRP are only 25% homologous, however, their active C-terminal regions are approximately 40% homologous, with nine out of the 10 Cys residues spatially conserved. Until now, 3D structures have not been available for either agouti, AGRP or their C-terminal regions. The NMR structure of MARP reported here can be characterized as three major loops, with four of the five disulfide bridges at the base of the structure. Though its fold is well defined, no canonical secondary structure is identified. While previously reported structural models of the C-terminal region of AGRP were attempted based on Cys homology between AGRP and certain toxin proteins, we find that Cys spacing is not sufficient to correctly determine the 3D fold of the molecule. | ||
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| - | NMR structure of a minimized human agouti related protein prepared by total chemical synthesis.,Bolin KA, Anderson DJ, Trulson JA, Thompson DA, Wilken J, Kent SB, Gantz I, Millhauser GL FEBS Lett. 1999 May 21;451(2):125-31. PMID:10371151<ref>PMID:10371151</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 1hyk" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Anderson | + | [[Category: Anderson DJ]] |
| - | [[Category: Bolin | + | [[Category: Bolin KA]] |
| - | [[Category: Kent | + | [[Category: Kent SBH]] |
| - | [[Category: Millhauser | + | [[Category: Millhauser GL]] |
| - | [[Category: Thompson | + | [[Category: Thompson DA]] |
| - | [[Category: Trulson | + | [[Category: Trulson JA]] |
| - | [[Category: Wilken | + | [[Category: Wilken J]] |
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Current revision
AGOUTI-RELATED PROTEIN (87-132) (AC-AGRP(87-132))
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