Structural-functional analysis of the third transmembrane domain of the corticotropin-releasing factor type 1 receptor role in activation and allosteric antagonism

Katerina Spyridaki, Minos Timotheos Matsoukas, Arnau Cordomi, Kostas Gkountelias, Maria Papadokostaki, Thomas Mavromoustakos, Diomedes E. Logothetis, Andrew N. Margioris, Leonardo Pardo, George Liapakis

Research output: Contribution to journalArticleResearchpeer-review

18 Citations (Scopus)

Abstract

Background: The molecular mechanisms underlying activation of CRF1 receptor (CRF1R) were elusive. Results: We determined specific residues in the transmembrane domains (TMs) of CRF1R that are critical for receptor activation. Conclusion: A possible "transmission switch" involving TM interactions is important for CRF1R activation. Significance: This knowledge may aid in the development of nonpeptide CRF1R antagonists for use in stress-related disorders. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
Original languageEnglish
Pages (from-to)18966-18977
JournalJournal of Biological Chemistry
Volume289
Issue number27
DOIs
Publication statusPublished - 4 Jul 2014

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