title: Novel Structural Approaches to Study GPCR Regulation.
abstract: BACKGROUND
  Upon natural agonist or pharmacological stimulation, G protein-coupled receptors (GPCRs) are subjected to posttranslational modifications, such as phosphorylation and ubiquitination. These posttranslational modifications allow protein-protein interactions that turn off and/or switch receptor signaling as well as trigger receptor internalization, recycling or degradation, among other responses. Characterization of these processes is essential to unravel the function and regulation of GPCR.
  
  
  METHODS
  In silico analysis and methods such as mass spectrometry have emerged as novel powerful tools. Both approaches have allowed proteomic studies to detect not only GPCR posttranslational modifications and receptor association with other signaling macromolecules but also to assess receptor conformational dynamics after ligand (agonist/antagonist) association.
  
  
  RESULTS
  this review aims to provide insights into some of these methodologies and to highlight how their use is enhancing our comprehension of GPCR function. We present an overview using data from different laboratories (including our own), particularly focusing on free fatty acid receptor 4 (FFA4) (previously known as GPR120) and α1A- and α1D-adrenergic receptors. From our perspective, these studies contribute to the understanding of GPCR regulation and will help to design better therapeutic agents.
authors.affiliation: Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ciudad Universitaria, Ciudad de México 04510, Mexico. malfme@gmail.com.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Alfonzo-Méndez
authors.affiliation: Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ciudad Universitaria, Ciudad de México 04510, Mexico. ralcanta@ifc.unam.mx.
authors.forename: Rocío
authors.initials: R
authors.lastname: Alcántara-Hernández
authors.affiliation: Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ciudad Universitaria, Ciudad de México 04510, Mexico. agarcia@ifc.unam.mx.
authors.forename: J Adolfo
authors.initials: JA
authors.lastname: García-Sáinz
mesh_terms: D000818:Animals; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D043562:Receptors, G-Protein-Coupled
keywords: FFA4; G protein-coupled receptors (GPCRs); GPR120; mass spectrometry (MS); phosphorylation; posttranslational modifications; protein–protein interactions; ubiquitination; α1-adrenoceptors