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Understanding the Structural Basis of Adhesion GPCR Functions

  • Demet Araç
  • Norbert Sträter
  • Elena Seiradake
Chapter
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 234)

Graphical Abstract

Abstract

Unlike conventional G-protein-coupled receptors (GPCRs), adhesion GPCRs (aGPCRs) have large extracellular regions that are autoproteolytically cleaved from their membrane-embedded seven-pass transmembrane helices. Autoproteolysis occurs within the conserved GPCR-Autoproteolysis INducing (GAIN) domain that is juxtaposed to the transmembrane domain and cleaves the last beta strand of the GAIN domain. The other domains of the extracellular region are variable and specific to each aGPCR and are likely involved in adhering to various ligands. Emerging evidence suggest that extracellular regions may modulate receptor function and that ligand binding to the extracellular regions may induce receptor activation via multiple mechanisms. Here, we summarize current knowledge about the structural understanding for the extracellular regions of aGPCRs and discuss their possible functional roles that emerge from the available structural information.

Keywords

GAIN Horm Olfactomedin Lectin Stachel Tethered agonist Unc5 FLRT Super-complex Latrophilin 

Notes

Acknowledgments

We would like to thank Gabriel Salzman (University of Chicago) for his help with some of the figures and critical reading of the manuscript. Supported by grants from the Brain Research Foundation (to D.A.) and Big Ideas Generator (to D.A.). N.S. thanks the Deutsche Forschungsgemeinschaft for support in the Research Unit 2149 (Project 5, STR 477/15-1). E.S. was supported by the UK Medical Research Council (MR/L018039/1).

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Copyright information

© Springer International Publishing AG 2016

Authors and Affiliations

  • Demet Araç
    • 1
  • Norbert Sträter
    • 2
  • Elena Seiradake
    • 3
  1. 1.Department of Biochemistry and Molecular BiologyUniversity of ChicagoChicagoUSA
  2. 2.Institute for Bioanalytical Chemistry, Leipzig UniversityLeipzigGermany
  3. 3.Department of BiochemistryUniversity of OxfordOxfordUK

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