Alanine scanning mutagenesis of the second extracellular loop of type 1 corticotropin-releasing factor receptor revealed residues critical for peptide binding

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dc.contributor.authorGkountelias, K.en
dc.contributor.authorTselios, T.en
dc.contributor.authorVenihaki, M.en
dc.contributor.authorDeraos, G.en
dc.contributor.authorLazaridis, I.en
dc.contributor.authorRassouli, O.en
dc.contributor.authorGravanis, A.en
dc.contributor.authorLiapakis, G.en
dc.date.accessioned2015-11-24T19:37:10Z
dc.date.available2015-11-24T19:37:10Z
dc.identifier.issn1521-0111-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/23997
dc.rightsDefault Licence-
dc.subjectAlanine/*geneticsen
dc.subjectAmino Acid Sequenceen
dc.subjectAmphibian Proteins/chemistry/genetics/metabolismen
dc.subjectBinding, Competitive/geneticsen
dc.subjectCell Lineen
dc.subjectHumansen
dc.subjectMolecular Sequence Dataen
dc.subjectMultigene Familyen
dc.subject*Mutagenesis, Site-Directeden
dc.subjectPeptide Fragments/chemistry/*genetics/*metabolismen
dc.subjectPeptide Hormones/chemistry/genetics/metabolismen
dc.subjectProtein Binding/geneticsen
dc.subjectProtein Structure, Tertiary/geneticsen
dc.subjectReceptors, Corticotropin-Releasing Hormone/chemistry/genetics/*metabolismen
dc.titleAlanine scanning mutagenesis of the second extracellular loop of type 1 corticotropin-releasing factor receptor revealed residues critical for peptide bindingen
heal.abstractUpon binding of the corticotropin-releasing factor (CRF) analog sauvagine to the type 1 CRF receptor (CRF(1)), the amino-terminal portion of the peptide has been shown to lie near Lys257 in the receptor's second extracellular loop (EL2). To test the hypothesis that EL2 residues play a role in the binding of sauvagine to CRF(1) we carried out an alanine-scanning mutagenesis study to determine the functional role of EL2 residues (Leu251 to Val266). Only the W259A, F260A, and W259A/F260A mutations reduced the binding affinity and potency of sauvagine. In contrast, these mutations did not seem to significantly alter the overall receptor conformation, in that they left unchanged the affinities of the ligands astressin and antalarmin that have been suggested to bind to different regions of CRF(1). The W259A, F260A, and W259A/F260A mutations also decreased the affinity of the endogenous ligand, CRF, implying that these residues may play a common important role in the binding of different peptides belonging to CRF family. Parallel amino acid deletions of the two peptides produced ligands with various affinities for wild-type CRF(1) compared with the W259A, F260A, and W259A/F260A mutants, supporting the interaction between the amino-terminal residues 8 to 10 of sauvagine and the corresponding region in CRF with EL2 of CRF(1). This is the first time that a specific region of CRF(1) has been implicated in detailed interactions between the receptor and the amino-terminal portion of peptides belonging to the CRF family.en
heal.accesscampus-
heal.fullTextAvailabilityTRUE-
heal.identifier.primary10.1124/mol.108.052423-
heal.identifier.secondaryhttp://www.ncbi.nlm.nih.gov/pubmed/19124613-
heal.identifier.secondaryhttp://molpharm.aspetjournals.org/content/75/4/793.full.pdf-
heal.journalNameMol Pharmacolen
heal.journalTypepeer-reviewed-
heal.languageen-
heal.publicationDate2009-
heal.recordProviderΠανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικήςel
heal.typejournalArticle-
heal.type.elΆρθρο Περιοδικούel
heal.type.enJournal articleen

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