% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Capaldi:860921,
      author       = {Capaldi, Stefano and Suku, Eda and Antolini, Martina and Di
                      Giacobbe, Mattia and Giorgetti, Alejandro and Buffelli,
                      Mario},
      title        = {{A}llosteric sodium binding cavity in {GPR}3: a novel
                      player in modulation of {A}β production},
      journal      = {Scientific reports},
      volume       = {8},
      number       = {1},
      issn         = {2045-2322},
      address      = {[London]},
      publisher    = {Macmillan Publishers Limited, part of Springer Nature},
      reportid     = {FZJ-2019-01573},
      pages        = {11102},
      year         = {2018},
      abstract     = {The orphan G-protein coupled receptor 3 (GPR3) belongs to
                      class A G-protein coupled receptors (GPCRs) and is highly
                      expressed in central nervous system neurons. Among other
                      functions, it is likely associated with neuron
                      differentiation and maturation. Recently, GPR3 has also been
                      linked to the production of Aβ peptides in neurons.
                      Unfortunately, the lack of experimental structural
                      information for this receptor hampers a deep
                      characterization of its function. Here, using an in-silico
                      and in-vitro combined approach, we describe, for the first
                      time, structural characteristics of GPR3 receptor underlying
                      its function: the agonist binding site and the allosteric
                      sodium binding cavity. We identified and validated by
                      alanine-scanning mutagenesis the role of three functionally
                      relevant residues: Cys2676.55, Phe1203.36 and Asp2.50. The
                      latter, when mutated into alanine, completely abolished the
                      constitutive and agonist-stimulated adenylate cyclase
                      activity of GPR3 receptor by disrupting its sodium binding
                      cavity. Interestingly, this is correlated with a decrease in
                      Aβ production in a model cell line. Taken together, these
                      results suggest an important role of the allosteric sodium
                      binding site for GPR3 activity and open a possible avenue
                      for the modulation of Aβ production in the Alzheimer's
                      Disease.},
      cin          = {IAS-5 / INM-9},
      ddc          = {600},
      cid          = {I:(DE-Juel1)IAS-5-20120330 / I:(DE-Juel1)INM-9-20140121},
      pnm          = {574 - Theory, modelling and simulation (POF3-574)},
      pid          = {G:(DE-HGF)POF3-574},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:30038319},
      UT           = {WOS:000439421600070},
      doi          = {10.1038/s41598-018-29475-7},
      url          = {https://juser.fz-juelich.de/record/860921},
}