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

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.