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Trends Biochem Sci. 2009 Jun;34(6):303-10. doi: 10.1016/j.tibs.2009.02.004. Epub 2009 May 14.

Passing the baton in class B GPCRs: peptide hormone activation via helix induction?

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Institut für Biochemie und Biotechnologie, Martin-Luther-Universität Halle-Wittenberg, Kurt-Mothes-Strasse 3, D-06120 Halle (Saale), Germany.


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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