title: Family B G Protein-coupled Receptors and their Ligands: From Structure to Function.
abstract: BACKGROUND
  Family B G protein-coupled receptors (GPCRs) play an important role in many physiological and pathophysiological processes. They are plasma-membrane proteins containing an extracellular N-domain, an intracellular C-tail, seven transmembrane domains (TMs), three extracellular (ELs) and three intracellular (ILs) loops.
  
  
  OBJECTIVE
  This review aims to summarize the current structural and functional information for family B GPCRs and their ligands, as well as, their physiological and pathophysiological role.
  
  
  METHODS
  Α thorough search of bibliographic databases for peer-reviewed research literature was undertaken. Moreover, molecular models of family B GPCRs were constructed and a structural alignment of their amino acid sequences was performed to demonstrate common structural characteristics.
  
  
  RESULTS
  In this review the family B GPCRs and their complexes with the receptor activity modifying proteins (RAMPs) were classified into five groups and the important physiological and pathophysiological role of these receptors was summarized. In addition, conserved residues of the Ndomain and the TMs of these receptors were numbered, thus making feasible the comparison of receptor structures and demonstrating common structural characteristics that are functionally important for all family B receptors. Molecular models created in this study were used to discuss the molecular mechanisms underlying ligand binding to family B GPCRs and receptor activation.
  
  
  CONCLUSIONS
  The findings of this review provide information about the structural-functional determinants of family B GPCRs and their ligands, thus boosting the design of novel drugs with better potencies and bioavailabilities, which might enrich the therapeutic armory for the treatment of a wide spectrum of family B GPCRs-related disorders.
authors.affiliation: Department of Pharmacology, School of Medicine, University of Crete, Voutes, Heraklion, 71003, Crete. Greece.
authors.forename: George
authors.initials: G
authors.lastname: Liapakis
authors.affiliation: Department of Pharmacy, University of Patras, 26500, Patras. Greece.
authors.forename: Minos-Timotheos
authors.initials: MT
authors.lastname: Matsoukas
authors.affiliation: Department of Pharmacology, School of Medicine, University of Crete, Heraklion, Crete. Greece.
authors.forename: Vlasios
authors.initials: V
authors.lastname: Karageorgos
authors.affiliation: Department of Clinical Chemistry, School of Medicine, University of Crete, Heraklion, Crete. Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Venihaki
authors.affiliation: Laboratory of Organic Chemistry, Department of Chemistry, University of Athens, Athens 11571. Greece.
authors.forename: Thomas
authors.initials: T
authors.lastname: Mavromoustakos
mesh_terms: D000494:Allosteric Regulation; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008024:Ligands; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D008024:Ligands; D010455:Peptides; D043562:Receptors, G-Protein-Coupled
keywords: Family B GPCRs; antagonists; binding; ligands; physiological/
  pathophysiological role; receptor activation; signaling; structure