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New page: '''Unreleased structure''' The entry 6d1u is ON HOLD Authors: Description: Category: Unreleased Structures
 
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'''Unreleased structure'''


The entry 6d1u is ON HOLD
==Crystal structure of the human CLR:RAMP1 extracellular domain heterodimer in complex with adrenomedullin 2/intermedin==
<StructureSection load='6d1u' size='340' side='right'caption='[[6d1u]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6d1u]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_O157:H7 Escherichia coli O157:H7] 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=6D1U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6D1U FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.05&#8491;</td></tr>
<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=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=PRD_900001:alpha-maltose'>PRD_900001</scene></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=6d1u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d1u OCA], [https://pdbe.org/6d1u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6d1u RCSB], [https://www.ebi.ac.uk/pdbsum/6d1u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6d1u ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ADM2_HUMAN ADM2_HUMAN] May play a role as physiological regulators of gastrointestinal, cardiovascular bioactivities mediated by the CALCRL/RAMPs receptor complexes. Activates the cAMP-dependent pathway.<ref>PMID:14615490</ref>  May play a role as physiological regulators of gastrointestinal, cardiovascular bioactivities mediated by the CALCRL/RAMPs receptor complexes. Activates the cAMP-dependent pathway.<ref>PMID:14615490</ref>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The cardioprotective vasodilator peptide adrenomedullin 2/intermedin (AM2/IMD) and the related adrenomedullin (AM) and calcitonin gene-related peptide (CGRP) signal through three heterodimeric receptors comprising the calcitonin receptor-like class B G protein-coupled receptor (CLR) and a variable receptor activity modifying protein (RAMP1, -2, or -3) that determines ligand selectivity. The CGRP receptor (RAMP1:CLR) favors CGRP binding, whereas the AM1 (RAMP2:CLR) and AM2 (RAMP3:CLR) receptors favor AM binding. How AM2/IMD binds the receptors and how RAMPs modulate its binding is unknown. Here, we show that AM2/IMD binds the three purified RAMP-CLR extracellular domain (ECD) complexes with a selectivity profile that is distinct from those of CGRP and AM. AM2/IMD bound all three ECD complexes, but preferred the CGRP and AM2 receptor complexes. A 2.05 A resolution crystal structure of an AM2/IMD antagonist fragment-bound RAMP1-CLR ECD complex revealed that AM2/IMD binds the complex through a unique triple beta-turn conformation that was confirmed by peptide and receptor mutagenesis. Comparisons of the receptor-bound conformations of AM2/IMD, AM, and a high-affinity CGRP analog revealed differences that may have implications for biased signaling. Guided by the structure, enhanced-affinity AM2/IMD antagonist variants were developed, including one that discriminates the AM1 and AM2 receptors with ~40-fold difference in affinities and one stabilized by an intramolecular disulfide bond. These results reveal differences in how the three peptides engage the receptors, inform development of AM2/IMD-based pharmacological tools and therapeutics, and provide insights into RAMP modulation of receptor pharmacology.


Authors:  
Structure-function analyses reveal a triple beta-turn receptor-bound conformation of adrenomedullin 2/intermedin and enable peptide antagonist design.,Roehrkasse AM, Booe JM, Lee SM, Warner ML, Pioszak AA J Biol Chem. 2018 Aug 23. pii: RA118.005062. doi: 10.1074/jbc.RA118.005062. PMID:30139742<ref>PMID:30139742</ref>


Description:  
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
<div class="pdbe-citations 6d1u" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli O157:H7]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Pioszak A]]
[[Category: Roehrkasse A]]
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