Tethered Agonism: A Common Activation Mechanism of Adhesion GPCRs.
Adhesion GPCRs harbor a tethered agonist sequence (reproduced from [24]) As the past years have seen a magnificent increase in knowledge on adhesion GPCR (aGPCR) signal transduction, the time had come to fill the gap on how these receptors can be activated. Based on experimental observations that deletion of the ectodomain can induce signaling, the idea arose that aGPCRs, just like other atypical GPCRs, may harbor a tethered agonist sequence. In this chapter, we describe the recent findings and characteristics of this agonist, called the Stachel sequence, and discuss potential mechanisms that cause liberation of this encrypted sequence. Further, we provide perspectives for application of Stachel-derived synthetic peptides in future studies of aGPCR function.
Medical Faculty, Institute of Biochemistry, University Leipzig, Johannisallee 30, Leipzig, 04103, Germany. ines.liebscher@medizin.uni-leipzig.de.
Ines
I
Liebscher
Medical Faculty, Institute of Biochemistry, University Leipzig, Johannisallee 30, Leipzig, 04103, Germany.
Torsten
T
Schöneberg
D000818:Animals; D001665:Binding Sites; D002448:Cell Adhesion / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction; D013329:Structure-Activity Relationship
D010455:Peptides; D043562:Receptors, G-Protein-Coupled
Activation mechanism; Adhesion GPCR; Peptide agonist; Signal transduction; Tethered agonism