FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2964598535> ?p ?o ?g. }

• W2964598535 endingPage "13223" @default.
• W2964598535 startingPage "13218" @default.
• W2964598535 abstract "A hallmark of G-protein–coupled receptors (GPCRs) is the conversion of external stimuli into specific cellular responses. In this tightly-regulated process, extracellular ligand binding by GPCRs promotes specific conformational changes within the seven transmembrane helices, leading to the coupling and activation of intracellular “transducer” proteins, such as heterotrimeric G proteins. Much of our understanding of the molecular mechanisms that govern GPCR activation is derived from experiments with purified receptors reconstituted in detergent micelles. To elucidate the influence of the phospholipid bilayer on GPCR activation, here we interrogated the functional, pharmacological, and biophysical properties of a GPCR, the β2-adrenergic receptor (β2AR), in high-density lipoprotein (HDL) particles. Compared with detergent-reconstituted β2AR, the β2AR in HDL particles had greatly enhanced levels of basal (constitutive) activity and displayed increased sensitivity to agonist activation, as assessed by activation of heterotrimeric G protein and allosteric coupling between the ligand-binding and transducer-binding pockets. Using 19F NMR spectroscopy, we directly linked these functional differences in detergent- and HDL-reconstituted β2AR to a change in the equilibrium between inactive and active receptor states. The contrast between the low levels of β2AR constitutive activity in cells and the high constitutive activity observed in an isolated phospholipid bilayer indicates that β2AR basal activity depends on the reconstitution system and further suggests that various cellular mechanisms suppress β2AR basal activity physiologically. Our findings provide critical additional insights into GPCR activation and reveal how dramatically reconstitution systems can impact membrane protein function. A hallmark of G-protein–coupled receptors (GPCRs) is the conversion of external stimuli into specific cellular responses. In this tightly-regulated process, extracellular ligand binding by GPCRs promotes specific conformational changes within the seven transmembrane helices, leading to the coupling and activation of intracellular “transducer” proteins, such as heterotrimeric G proteins. Much of our understanding of the molecular mechanisms that govern GPCR activation is derived from experiments with purified receptors reconstituted in detergent micelles. To elucidate the influence of the phospholipid bilayer on GPCR activation, here we interrogated the functional, pharmacological, and biophysical properties of a GPCR, the β2-adrenergic receptor (β2AR), in high-density lipoprotein (HDL) particles. Compared with detergent-reconstituted β2AR, the β2AR in HDL particles had greatly enhanced levels of basal (constitutive) activity and displayed increased sensitivity to agonist activation, as assessed by activation of heterotrimeric G protein and allosteric coupling between the ligand-binding and transducer-binding pockets. Using 19F NMR spectroscopy, we directly linked these functional differences in detergent- and HDL-reconstituted β2AR to a change in the equilibrium between inactive and active receptor states. The contrast between the low levels of β2AR constitutive activity in cells and the high constitutive activity observed in an isolated phospholipid bilayer indicates that β2AR basal activity depends on the reconstitution system and further suggests that various cellular mechanisms suppress β2AR basal activity physiologically. Our findings provide critical additional insights into GPCR activation and reveal how dramatically reconstitution systems can impact membrane protein function." @default.
• W2964598535 created "2019-08-13" @default.
• W2964598535 creator A5027483743 @default.
• W2964598535 creator A5032543179 @default.
• W2964598535 creator A5073548504 @default.
• W2964598535 creator A5080672788 @default.
• W2964598535 creator A5081800434 @default.
• W2964598535 date "2019-09-01" @default.
• W2964598535 modified "2023-09-27" @default.
• W2964598535 title "Detergent- and phospholipid-based reconstitution systems have differential effects on constitutive activity of G-protein–coupled receptors" @default.
• W2964598535 cites W1962808243 @default.
• W2964598535 cites W1991163722 @default.
• W2964598535 cites W2020601776 @default.
• W2964598535 cites W2023724239 @default.
• W2964598535 cites W2064253637 @default.
• W2964598535 cites W2077425788 @default.
• W2964598535 cites W2078108096 @default.
• W2964598535 cites W2102459914 @default.
• W2964598535 cites W2107492651 @default.
• W2964598535 cites W2133354537 @default.
• W2964598535 cites W2136716118 @default.
• W2964598535 cites W2139129258 @default.
• W2964598535 cites W2153502397 @default.
• W2964598535 cites W2200539429 @default.
• W2964598535 cites W2216747556 @default.
• W2964598535 cites W2345966590 @default.
• W2964598535 cites W2471992026 @default.
• W2964598535 cites W2604550827 @default.
• W2964598535 cites W2624652951 @default.
• W2964598535 cites W2763752752 @default.
• W2964598535 cites W2791362882 @default.
• W2964598535 doi "https://doi.org/10.1074/jbc.ac119.009848" @default.
• W2964598535 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6737212" @default.
• W2964598535 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31362983" @default.
• W2964598535 hasPublicationYear "2019" @default.
• W2964598535 type Work @default.
• W2964598535 sameAs 2964598535 @default.
• W2964598535 citedByCount "33" @default.
• W2964598535 countsByYear W29645985352020 @default.
• W2964598535 countsByYear W29645985352021 @default.
• W2964598535 countsByYear W29645985352022 @default.
• W2964598535 countsByYear W29645985352023 @default.
• W2964598535 crossrefType "journal-article" @default.
• W2964598535 hasAuthorship W2964598535A5027483743 @default.
• W2964598535 hasAuthorship W2964598535A5032543179 @default.
• W2964598535 hasAuthorship W2964598535A5073548504 @default.
• W2964598535 hasAuthorship W2964598535A5080672788 @default.
• W2964598535 hasAuthorship W2964598535A5081800434 @default.
• W2964598535 hasBestOaLocation W29645985351 @default.
• W2964598535 hasConcept C12554922 @default.
• W2964598535 hasConcept C135285700 @default.
• W2964598535 hasConcept C139407321 @default.
• W2964598535 hasConcept C166342909 @default.
• W2964598535 hasConcept C170493617 @default.
• W2964598535 hasConcept C185592680 @default.
• W2964598535 hasConcept C2778918659 @default.
• W2964598535 hasConcept C41625074 @default.
• W2964598535 hasConcept C55493867 @default.
• W2964598535 hasConcept C80631254 @default.
• W2964598535 hasConcept C86803240 @default.
• W2964598535 hasConcept C95444343 @default.
• W2964598535 hasConceptScore W2964598535C12554922 @default.
• W2964598535 hasConceptScore W2964598535C135285700 @default.
• W2964598535 hasConceptScore W2964598535C139407321 @default.
• W2964598535 hasConceptScore W2964598535C166342909 @default.
• W2964598535 hasConceptScore W2964598535C170493617 @default.
• W2964598535 hasConceptScore W2964598535C185592680 @default.
• W2964598535 hasConceptScore W2964598535C2778918659 @default.
• W2964598535 hasConceptScore W2964598535C41625074 @default.
• W2964598535 hasConceptScore W2964598535C55493867 @default.
• W2964598535 hasConceptScore W2964598535C80631254 @default.
• W2964598535 hasConceptScore W2964598535C86803240 @default.
• W2964598535 hasConceptScore W2964598535C95444343 @default.
• W2964598535 hasFunder F4320306082 @default.
• W2964598535 hasFunder F4320332161 @default.
• W2964598535 hasFunder F4320334506 @default.
• W2964598535 hasFunder F4320334593 @default.
• W2964598535 hasIssue "36" @default.
• W2964598535 hasLocation W29645985351 @default.
• W2964598535 hasLocation W29645985352 @default.
• W2964598535 hasOpenAccess W2964598535 @default.
• W2964598535 hasPrimaryLocation W29645985351 @default.
• W2964598535 hasRelatedWork W1199870172 @default.
• W2964598535 hasRelatedWork W1671856927 @default.
• W2964598535 hasRelatedWork W2034244767 @default.
• W2964598535 hasRelatedWork W2552525175 @default.
• W2964598535 hasRelatedWork W2795120659 @default.
• W2964598535 hasRelatedWork W3105780475 @default.
• W2964598535 hasRelatedWork W3137473376 @default.
• W2964598535 hasRelatedWork W4220968017 @default.
• W2964598535 hasRelatedWork W4246451705 @default.
• W2964598535 hasRelatedWork W4380449949 @default.
• W2964598535 hasVolume "294" @default.
• W2964598535 isParatext "false" @default.
• W2964598535 isRetracted "false" @default.
• W2964598535 magId "2964598535" @default.
• W2964598535 workType "article" @default.