Matches in SemOpenAlex for { <https://semopenalex.org/work/W2158599032> ?p ?o ?g. }
- W2158599032 endingPage "983" @default.
- W2158599032 startingPage "976" @default.
- W2158599032 abstract "Helix-8 (Hx8) is a structurally conserved amphipathic helical motif in class-A GPCRs, adjacent to the C-terminal sequence that is responsible for PDZ-domain-recognition. The Hx8 segment in the dopamine D2 receptor (D2R) constitutes the C-terminal segment and we investigate its role in the function of D2R by studying the interaction with the PDZ-containing GIPC1 using homology models based on the X-ray structures of very closely related analogs: the D3R for the D2R model, and the PDZ domain of GIPC2 for GIPC1–PDZ. The mechanism of this interaction was investigated with all-atom unbiased molecular dynamics (MD) simulations that reveal the role of the membrane in maintaining the helical fold of Hx8, and with biased MD simulations to elucidate the energy drive for the interaction with the GIPC1–PDZ. We found that it becomes more favorable energetically for Hx8 to adopt the extended conformation observed in all PDZ–ligand complexes when it moves away from the membrane, and that C-terminus palmitoylation of D2R enhanced membrane penetration by the Hx8 backbone. De-palmitoylation enables Hx8 to move out into the aqueous environment for interaction with the PDZ domain. All-atom unbiased MD simulations of the full D2R–GIPC1-PDZ complex in sphingolipid/cholesterol membranes show that the D2R carboxyl C-terminus samples the region of the conserved GFGL motif located on the carboxylate-binding loop of the GIPC1–PDZ, and the entire complex distances itself from the membrane interface. Together, these results outline a likely mechanism of Hx8 involvement in the interaction of the GPCR with PDZ-domains in the course of signaling." @default.
- W2158599032 created "2016-06-24" @default.
- W2158599032 creator A5014370221 @default.
- W2158599032 creator A5057659093 @default.
- W2158599032 date "2015-04-01" @default.
- W2158599032 modified "2023-10-18" @default.
- W2158599032 title "A mechanistic role of Helix 8 in GPCRs: Computational modeling of the dopamine D2 receptor interaction with the GIPC1–PDZ-domain" @default.
- W2158599032 cites W1908561802 @default.
- W2158599032 cites W1966041739 @default.
- W2158599032 cites W1974560738 @default.
- W2158599032 cites W1978310995 @default.
- W2158599032 cites W1979166300 @default.
- W2158599032 cites W1980823970 @default.
- W2158599032 cites W1980826665 @default.
- W2158599032 cites W1986986500 @default.
- W2158599032 cites W1989971979 @default.
- W2158599032 cites W1993735775 @default.
- W2158599032 cites W1996320892 @default.
- W2158599032 cites W1998729532 @default.
- W2158599032 cites W2035266068 @default.
- W2158599032 cites W2035687084 @default.
- W2158599032 cites W2042170152 @default.
- W2158599032 cites W2046111024 @default.
- W2158599032 cites W2048410843 @default.
- W2158599032 cites W2050333027 @default.
- W2158599032 cites W2055043387 @default.
- W2158599032 cites W2057806291 @default.
- W2158599032 cites W2060079863 @default.
- W2158599032 cites W2067990965 @default.
- W2158599032 cites W2068964976 @default.
- W2158599032 cites W2075676530 @default.
- W2158599032 cites W2080621111 @default.
- W2158599032 cites W2088365719 @default.
- W2158599032 cites W2094392932 @default.
- W2158599032 cites W2096994057 @default.
- W2158599032 cites W2104961861 @default.
- W2158599032 cites W2106648157 @default.
- W2158599032 cites W2107564139 @default.
- W2158599032 cites W2119267663 @default.
- W2158599032 cites W2122953898 @default.
- W2158599032 cites W2125345242 @default.
- W2158599032 cites W2129105333 @default.
- W2158599032 cites W2129130876 @default.
- W2158599032 cites W2133167066 @default.
- W2158599032 cites W2133179696 @default.
- W2158599032 cites W2137588110 @default.
- W2158599032 cites W2139325100 @default.
- W2158599032 cites W2149525061 @default.
- W2158599032 cites W2149963584 @default.
- W2158599032 cites W2150981663 @default.
- W2158599032 cites W2160536323 @default.
- W2158599032 cites W2163190470 @default.
- W2158599032 cites W2166384691 @default.
- W2158599032 cites W2167857702 @default.
- W2158599032 cites W2330260612 @default.
- W2158599032 cites W59871007 @default.
- W2158599032 doi "https://doi.org/10.1016/j.bbamem.2014.12.002" @default.
- W2158599032 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4336197" @default.
- W2158599032 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25592838" @default.
- W2158599032 hasPublicationYear "2015" @default.
- W2158599032 type Work @default.
- W2158599032 sameAs 2158599032 @default.
- W2158599032 citedByCount "36" @default.
- W2158599032 countsByYear W21585990322015 @default.
- W2158599032 countsByYear W21585990322016 @default.
- W2158599032 countsByYear W21585990322017 @default.
- W2158599032 countsByYear W21585990322018 @default.
- W2158599032 countsByYear W21585990322019 @default.
- W2158599032 countsByYear W21585990322020 @default.
- W2158599032 countsByYear W21585990322021 @default.
- W2158599032 countsByYear W21585990322022 @default.
- W2158599032 crossrefType "journal-article" @default.
- W2158599032 hasAuthorship W2158599032A5014370221 @default.
- W2158599032 hasAuthorship W2158599032A5057659093 @default.
- W2158599032 hasBestOaLocation W21585990321 @default.
- W2158599032 hasConcept C12554922 @default.
- W2158599032 hasConcept C135285700 @default.
- W2158599032 hasConcept C147597530 @default.
- W2158599032 hasConcept C154428179 @default.
- W2158599032 hasConcept C159110408 @default.
- W2158599032 hasConcept C169627665 @default.
- W2158599032 hasConcept C170493617 @default.
- W2158599032 hasConcept C181199279 @default.
- W2158599032 hasConcept C185592680 @default.
- W2158599032 hasConcept C41685203 @default.
- W2158599032 hasConcept C55493867 @default.
- W2158599032 hasConcept C59593255 @default.
- W2158599032 hasConcept C71924100 @default.
- W2158599032 hasConcept C86803240 @default.
- W2158599032 hasConceptScore W2158599032C12554922 @default.
- W2158599032 hasConceptScore W2158599032C135285700 @default.
- W2158599032 hasConceptScore W2158599032C147597530 @default.
- W2158599032 hasConceptScore W2158599032C154428179 @default.
- W2158599032 hasConceptScore W2158599032C159110408 @default.
- W2158599032 hasConceptScore W2158599032C169627665 @default.
- W2158599032 hasConceptScore W2158599032C170493617 @default.
- W2158599032 hasConceptScore W2158599032C181199279 @default.
- W2158599032 hasConceptScore W2158599032C185592680 @default.