PDZ domain-mediated interactions of G protein-coupled receptors with postsynaptic density protein 95: quantitative characterization of interactions.

G protein-coupled receptors (GPCRs) constitute the largest family of membrane proteins in the human genome. Their signaling is regulated by scaffold proteins containing PDZ domains, but although these interactions are important for GPCR function, they are still poorly understood. We here present a q...

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Autores principales:	Thor C Møller, Volker F Wirth, Nina I Roberts, Julia Bender, Anders Bach, Birgitte P S Jacky, Kristian Strømgaard, Jan M Deussing, Thue W Schwartz, Karen L Martinez
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a9defa479cb94c259cea6884cc9f692f
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spelling	oai:doaj.org-article:a9defa479cb94c259cea6884cc9f692f2021-11-18T07:45:51ZPDZ domain-mediated interactions of G protein-coupled receptors with postsynaptic density protein 95: quantitative characterization of interactions.1932-620310.1371/journal.pone.0063352https://doaj.org/article/a9defa479cb94c259cea6884cc9f692f2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23691031/?tool=EBIhttps://doaj.org/toc/1932-6203G protein-coupled receptors (GPCRs) constitute the largest family of membrane proteins in the human genome. Their signaling is regulated by scaffold proteins containing PDZ domains, but although these interactions are important for GPCR function, they are still poorly understood. We here present a quantitative characterization of the kinetics and affinity of interactions between GPCRs and one of the best characterized PDZ scaffold proteins, postsynaptic density protein 95 (PSD-95), using fluorescence polarization (FP) and surface plasmon resonance (SPR). By comparing these in vitro findings with colocalization of the full-length proteins in cells and with previous studies, we suggest that the range of relevant interactions might extend to interactions with K i = 450 µM in the in vitro assays. Within this range, we identify novel PSD-95 interactions with the chemokine receptor CXCR2, the neuropeptide Y receptor Y2, and four of the somatostatin receptors (SSTRs). The interaction with SSTR1 was further investigated in mouse hippocampal neurons, where we found a clear colocalization between the endogenously expressed proteins, indicating a potential for further investigation of the role of this interaction. The approach can easily be transferred to other receptors and scaffold proteins and this could help accelerate the discovery and quantitative characterization of GPCR-PDZ interactions.Thor C MøllerVolker F WirthNina I RobertsJulia BenderAnders BachBirgitte P S JackyKristian StrømgaardJan M DeussingThue W SchwartzKaren L MartinezPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 5, p e63352 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Thor C Møller Volker F Wirth Nina I Roberts Julia Bender Anders Bach Birgitte P S Jacky Kristian Strømgaard Jan M Deussing Thue W Schwartz Karen L Martinez PDZ domain-mediated interactions of G protein-coupled receptors with postsynaptic density protein 95: quantitative characterization of interactions.
description	G protein-coupled receptors (GPCRs) constitute the largest family of membrane proteins in the human genome. Their signaling is regulated by scaffold proteins containing PDZ domains, but although these interactions are important for GPCR function, they are still poorly understood. We here present a quantitative characterization of the kinetics and affinity of interactions between GPCRs and one of the best characterized PDZ scaffold proteins, postsynaptic density protein 95 (PSD-95), using fluorescence polarization (FP) and surface plasmon resonance (SPR). By comparing these in vitro findings with colocalization of the full-length proteins in cells and with previous studies, we suggest that the range of relevant interactions might extend to interactions with K i = 450 µM in the in vitro assays. Within this range, we identify novel PSD-95 interactions with the chemokine receptor CXCR2, the neuropeptide Y receptor Y2, and four of the somatostatin receptors (SSTRs). The interaction with SSTR1 was further investigated in mouse hippocampal neurons, where we found a clear colocalization between the endogenously expressed proteins, indicating a potential for further investigation of the role of this interaction. The approach can easily be transferred to other receptors and scaffold proteins and this could help accelerate the discovery and quantitative characterization of GPCR-PDZ interactions.
format	article
author	Thor C Møller Volker F Wirth Nina I Roberts Julia Bender Anders Bach Birgitte P S Jacky Kristian Strømgaard Jan M Deussing Thue W Schwartz Karen L Martinez
author_facet	Thor C Møller Volker F Wirth Nina I Roberts Julia Bender Anders Bach Birgitte P S Jacky Kristian Strømgaard Jan M Deussing Thue W Schwartz Karen L Martinez
author_sort	Thor C Møller
title	PDZ domain-mediated interactions of G protein-coupled receptors with postsynaptic density protein 95: quantitative characterization of interactions.
title_short	PDZ domain-mediated interactions of G protein-coupled receptors with postsynaptic density protein 95: quantitative characterization of interactions.
title_full	PDZ domain-mediated interactions of G protein-coupled receptors with postsynaptic density protein 95: quantitative characterization of interactions.
title_fullStr	PDZ domain-mediated interactions of G protein-coupled receptors with postsynaptic density protein 95: quantitative characterization of interactions.
title_full_unstemmed	PDZ domain-mediated interactions of G protein-coupled receptors with postsynaptic density protein 95: quantitative characterization of interactions.
title_sort	pdz domain-mediated interactions of g protein-coupled receptors with postsynaptic density protein 95: quantitative characterization of interactions.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/a9defa479cb94c259cea6884cc9f692f
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PDZ domain-mediated interactions of G protein-coupled receptors with postsynaptic density protein 95: quantitative characterization of interactions.

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