View source for 2kza


==Solution structure of ASIP(80-132, P103A, P105A, Q115Y, S124Y)==
<StructureSection load='2kza' size='340' side='right'caption='[[2kza]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2kza]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KZA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KZA FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</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=2kza FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kza OCA], [https://pdbe.org/2kza PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kza RCSB], [https://www.ebi.ac.uk/pdbsum/2kza PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kza ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ASIP_HUMAN ASIP_HUMAN] Involved in the regulation of melanogenesis. The binding of ASP to MC1R precludes alpha-MSH initiated signaling and thus blocks production of cAMP, leading to a down-regulation of eumelanogenesis (brown/black pigment) and thus increasing synthesis of pheomelanin (yellow/red pigment). In higher primates, agouti may affect the quality of hair pigmentation rather than its pattern of deposition. Could well play a role in neuroendocrine aspects of melanocortin action. May have some functional role in regulating the lipid metabolism with adipocytes.
== 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/kz/2kza_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=2kza ConSurf].
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== Publication Abstract from PubMed ==
Agouti-related protein (AgRP) and agouti signaling protein (ASIP) are homologs that play critical roles in energy balance and pigmentation, respectively, by functioning as antagonistic ligands at their cognate melanocortin receptors. Signaling specificity is mediated in part through receptor binding selectivity brought about by alterations in the cysteine-rich carboxy-terminal domains of the ligands. AgRP binds with high affinity to the melanocortin 3 receptor and the melanocortin 4 receptor, but not to the melanocortin 1 receptor (MC1R), whereas ASIP binds with high affinity to all three receptors. This work explores the structural basis for receptor selectivity by studying chimeric proteins developed by interchanging loops between the cysteine-rich domain of ASIP and the cysteine-rich domain of AgRP. Binding data demonstrate that melanocortin 4 receptor responds to all chimeras and is therefore highly tolerant of gross loop changes. By contrast, MC1R responds primarily to those chimeras with a sequence close to that of wild-type ASIP. Further analysis of binding and functional data suggests that the ASIP C-terminal loop (a six-amino-acid segment closed by the final disulfide bond) is essential for high-affinity MC1R binding and inverse agonism. Comparison with previously published molecular models suggests that this loop makes contact with the first extracellular loop of MC1R through a series of key hydrophobic interactions.

Loop-Swapped Chimeras of the Agouti-Related Protein and the Agouti Signaling Protein Identify Contacts Required for Melanocortin 1 Receptor Selectivity and Antagonism.,Patel MP, Cribb Fabersunne CS, Yang YK, Kaelin CB, Barsh GS, Millhauser GL J Mol Biol. 2010 Sep 8. PMID:20831872<ref>PMID:20831872</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2kza" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Barsh GS]]
[[Category: Cribb Fabersunne CS]]
[[Category: Kaelin CB]]
[[Category: Millhauser GL]]
[[Category: Patel MP]]
[[Category: Yang Y]]