Passing the baton in class B GPCRs: peptide hormone activation via helix induction?
2009; Elsevier BV; Volume: 34; Issue: 6 Linguagem: Inglês
10.1016/j.tibs.2009.02.004
ISSN1362-4326
AutoresC. Parthier, Steffen Reedtz‐Runge, Rainer Rudolph, Milton T. Stubbs,
Tópico(s)Protein Kinase Regulation and GTPase Signaling
ResumoG-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 α-helical structuring of the ligand. The latter suggests an attractive mechanical model for class B GPCR activation. 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 α-helical structuring of the ligand. The latter suggests an attractive mechanical model for class B GPCR activation.
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