Passing the baton in class B GPCRs: peptide hormone activation via helix induction?
Christoph Parthier1, Steffen Reedtz-Runge, Rainer Rudolph
1Institut für Biochemie und Biotechnologie, Martin-Luther-Universität Halle-Wittenberg, Kurt-Mothes-Strasse 3, D-06120 Halle (Saale), Germany. parthier@biochemtech.uni-halle.de
Abstract:
G-protein-coupled receptors (GPCRs) represent the largest constellation of validated drug targets. Crystal structures of class A GPCRs have facilitated major advances in understanding the principles underlying GPCR activation. By contrast, relatively little is known about class B GPCRs, a family of receptors for a variety of therapeutically relevant peptide hormones. Encouraging progress has recently been made through the structural elucidation of several extracellular hormone-binding domains of class B GPCRs in complex with their natural ligands or synthetic analogues. The structures reveal similar modes of ligand binding, with concomitant alpha-helical structuring of the ligand. The latter suggests an attractive mechanical model for class B GPCR activation.
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