000139938 001__ 139938
000139938 005__ 20210129212726.0
000139938 0247_ $$2doi$$a10.1111/bph.12118
000139938 0247_ $$2ISSN$$a0366-0826
000139938 0247_ $$2ISSN$$a1476-5381
000139938 0247_ $$2ISSN$$a0007-1188
000139938 0247_ $$2WOS$$aWOS:000317679000011
000139938 0247_ $$2Handle$$a2128/5643
000139938 037__ $$aFZJ-2013-05905
000139938 082__ $$a610
000139938 1001_ $$0P:(DE-HGF)0$$aWatkins, HA$$b0
000139938 245__ $$aIdentification of key residues involved in adrenomedullin binding to the AM 1 receptor
000139938 260__ $$aMalden, MA$$bWiley$$c2013
000139938 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s139938
000139938 3367_ $$2DataCite$$aOutput Types/Journal article
000139938 3367_ $$00$$2EndNote$$aJournal Article
000139938 3367_ $$2BibTeX$$aARTICLE
000139938 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000139938 3367_ $$2DRIVER$$aarticle
000139938 500__ $$3POF3_Assignment on 2016-02-29
000139938 520__ $$aBACKGROUND AND PURPOSE:Adrenomedullin (AM) is a peptide hormone whose receptors are members of the class B GPCR family. They comprise a heteromer between the GPCR, the calcitonin receptor-like receptor and one of the receptor activity-modifying proteins 1-3. AM plays a significant role in angiogenesis and its antagonist fragment AM22-52 can inhibit blood vessel and tumour growth. The mechanism by which AM interacts with its receptors is unknown.EXPERIMENTAL APPROACH:We determined the AM22-52 binding epitope for the AM1 receptor extracellular domain using biophysical techniques, heteronuclear magnetic resonance spectroscopy and alanine scanning.KEY RESULTS:Chemical shift perturbation experiments located the main binding epitope for AM22-52 at the AM1 receptor to the C-terminal 8 amino acids. Isothermal titration calorimetry of AM22-52 alanine-substituted peptides indicated that Y52, G51 and I47 are essential for AM1 receptor binding and that K46 and P49 and R44 have a smaller role to play. Characterization of these peptides at the full-length AM receptors was assessed in Cos7 cells by cAMP assay. This confirmed the essential role of Y52, G51 and I47 in binding to the AM1 receptor, with their substitution resulting in ≥100-fold reduction in antagonist potency compared with AM22-52 . R44A, K46A, S48A and P49A AM22-52 decreased antagonist potency by approximately 10-fold.CONCLUSIONS AND IMPLICATIONS:This study localizes the main binding epitope of AM22-52 to its C-terminal amino acids and distinguishes essential residues involved in this binding. This will inform the development of improved AM receptor antagonists.
000139938 536__ $$0G:(DE-HGF)POF2-452$$a452 - Structural Biology (POF2-452)$$cPOF2-452$$fPOF II$$x0
000139938 588__ $$aDataset connected to CrossRef, juser.fz-juelich.de
000139938 7001_ $$0P:(DE-HGF)0$$aAu, M$$b1
000139938 7001_ $$0P:(DE-HGF)0$$aBobby, R$$b2
000139938 7001_ $$0P:(DE-HGF)0$$aArchbold, JK$$b3
000139938 7001_ $$0P:(DE-HGF)0$$aAbdul-Manan, N$$b4
000139938 7001_ $$0P:(DE-HGF)0$$aMoore, JM$$b5
000139938 7001_ $$0P:(DE-HGF)0$$aMiddleditch, MJ$$b6
000139938 7001_ $$0P:(DE-HGF)0$$aWilliams, GM$$b7
000139938 7001_ $$0P:(DE-HGF)0$$aBrimble, MA$$b8
000139938 7001_ $$0P:(DE-Juel1)145681$$aDingley, Andrew$$b9
000139938 7001_ $$0P:(DE-HGF)0$$aHay, DL$$b10$$eCorresponding author
000139938 773__ $$0PERI:(DE-600)2029728-2$$a10.1111/bph.12118$$gVol. 169, no. 1, p. 143 - 155$$n1$$p143 - 155$$tBritish journal of pharmacology$$v169$$x0007-1188$$y2013
000139938 8564_ $$uhttp://www.ncbi.nlm.nih.gov/pubmed/23351143
000139938 8564_ $$uhttps://juser.fz-juelich.de/record/139938/files/FZJ-2013-05905.pdf$$yOpenAccess$$zPublished final document.
000139938 8564_ $$uhttps://juser.fz-juelich.de/record/139938/files/FZJ-2013-05905.jpg?subformat=icon-144$$xicon-144$$yOpenAccess
000139938 8564_ $$uhttps://juser.fz-juelich.de/record/139938/files/FZJ-2013-05905.jpg?subformat=icon-180$$xicon-180$$yOpenAccess
000139938 8564_ $$uhttps://juser.fz-juelich.de/record/139938/files/FZJ-2013-05905.jpg?subformat=icon-640$$xicon-640$$yOpenAccess
000139938 909CO $$ooai:juser.fz-juelich.de:139938$$pdnbdelivery$$pVDB$$pdriver$$popen_access$$popenaire
000139938 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)145681$$aForschungszentrum Jülich GmbH$$b9$$kFZJ
000139938 9132_ $$0G:(DE-HGF)POF3-559H$$1G:(DE-HGF)POF3-550$$2G:(DE-HGF)POF3-500$$aDE-HGF$$bKey Technologies$$lBioSoft – Fundamentals for future Technologies in the fields of Soft Matter and Life Sciences$$vAddenda$$x0
000139938 9131_ $$0G:(DE-HGF)POF2-452$$1G:(DE-HGF)POF2-450$$2G:(DE-HGF)POF2-400$$3G:(DE-HGF)POF2$$4G:(DE-HGF)POF$$aDE-HGF$$bSchlüsseltechnologien$$lBioSoft$$vStructural Biology$$x0
000139938 9141_ $$y2013
000139938 915__ $$0StatID:(DE-HGF)0010$$2StatID$$aJCR/ISI refereed
000139938 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR
000139938 915__ $$0StatID:(DE-HGF)0110$$2StatID$$aWoS$$bScience Citation Index
000139938 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded
000139938 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection
000139938 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bThomson Reuters Master Journal List
000139938 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS
000139938 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline
000139938 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database
000139938 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess
000139938 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences
000139938 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews
000139938 920__ $$lyes
000139938 9201_ $$0I:(DE-Juel1)ICS-6-20110106$$kICS-6$$lStrukturbiochemie $$x0
000139938 9801_ $$aFullTexts
000139938 980__ $$ajournal
000139938 980__ $$aUNRESTRICTED
000139938 980__ $$aFullTexts
000139938 980__ $$aI:(DE-Juel1)ICS-6-20110106
000139938 980__ $$aVDB
000139938 981__ $$aI:(DE-Juel1)IBI-7-20200312