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Conformational changes in G‐protein‐coupled receptors—the quest for functionally selective conformations is open
Author(s) -
Hoffmann C,
Zürn A,
Bünemann M,
Lohse M J
Publication year - 2008
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0707615
Subject(s) - g protein coupled receptor , receptor , effector , conformational change , agonist , g protein , chemistry , computational biology , protein structure , drug discovery , biophysics , biology , stereochemistry , biochemistry
The G‐protein‐coupled receptors (GPCRs) represent one the largest families of drug targets. Upon agonist binding a receptor undergoes conformational rearrangements that lead to a novel protein conformation which in turn can interact with effector proteins. During the last decade significant progress has been made to prove that different conformational changes occur. Today it is mostly accepted that individual ligands can induce different receptor conformations. However, the nature or molecular identity of the different conformations is still ill‐known. Knowledge of the potential functionally selective conformations will help to develop drugs that select specific conformations of a given GPCR which couple to specific signalling pathways and may, ultimately, lead to reduced side effects. In this review we will summarize recent progress in biophysical approaches that have led to the current understanding of conformational changes that occur during GPCR activation. British Journal of Pharmacology (2008) 153 , S358–S366; doi: 10.1038/sj.bjp.0707615 ; published online 3 December 2007