Matches in SemOpenAlex for { <https://semopenalex.org/work/W2001885803> ?p ?o ?g. }
Showing items 1 to 63 of
63
with 100 items per page.
- W2001885803 endingPage "211a" @default.
- W2001885803 startingPage "210a" @default.
- W2001885803 abstract "The PLB monomer inhibits the Ca2+ pump of cardiac sarcoplasmic reticulum (SERCA2a) by decreasing the apparent Ca2+ affinity of the enzyme. Here we addressed the molecular mechanism of enzyme inhibition using a PLB triple-mutant, N27A, N30C, L37A-PLB (PLB3), which is a potent gain-of-function PLB mutant that is cross-linkable to SERCA2a at Lys328. We observed that the protein-protein interaction between PLB3 and SERCA2a was strictly Ca2+-dependent and that several fold higher Ca2+ concentrations were required to both dissociate PLB3 from SERCA2a and to stimulate Ca2+-ATPase activity. The results suggest that PLB inhibits SERCA2a activity by competing directly for Ca2+ binding to the enzyme and that PLB must completely dissociate from SERCA2a for enzyme activation to occur. To test this hypothesis further, we co-expressed PLB3 with D351A-SERCA2a, a Ca2+ pump mutant that is inactivated at the site of ATP hydrolysis in the cytoplasm, but which retains the two high affinity Ca2+ binding sites in the membrane and maintains the thermodynamic equilibrium between E1 (high Ca2+ affinity state) and E2 (low Ca2+ affinity state). Remarkably, the affinity of D351A for Ca2+ was increased 30-fold relative to that of WT-SERCA2a, demonstrating a robust, long-range communication between the ATP hydrolysis site in the cytoplasm and the Ca2+ binding sites in the membrane. Nonetheless, PLB3 continued to bind strongly to D351A, and several fold higher Ca2+ concentrations were required to dissociate PLB3 from D351A compared to PLB molecules with normal function. Our results strongly support our model in which PLB binds to one unique conformation of SERCA2a, the Ca2+ free, E2 conformation stabilized by bound nucleotide. For both WT-SERCA2a and D351A, PLB lowers the Ca2+ binding affinity of the enzyme by stabilizing E2 thereby blocking the transition to E1." @default.
- W2001885803 created "2016-06-24" @default.
- W2001885803 creator A5004272413 @default.
- W2001885803 creator A5018874505 @default.
- W2001885803 creator A5027046296 @default.
- W2001885803 date "2009-02-01" @default.
- W2001885803 modified "2023-09-26" @default.
- W2001885803 title "Cross-Linkable, Gain-of-Function Phospholamban (PLB) Mutant Reveals the Molecular Mechanism of SERCA2a Inhibition" @default.
- W2001885803 doi "https://doi.org/10.1016/j.bpj.2008.12.1865" @default.
- W2001885803 hasPublicationYear "2009" @default.
- W2001885803 type Work @default.
- W2001885803 sameAs 2001885803 @default.
- W2001885803 citedByCount "0" @default.
- W2001885803 crossrefType "journal-article" @default.
- W2001885803 hasAuthorship W2001885803A5004272413 @default.
- W2001885803 hasAuthorship W2001885803A5018874505 @default.
- W2001885803 hasAuthorship W2001885803A5027046296 @default.
- W2001885803 hasBestOaLocation W20018858031 @default.
- W2001885803 hasConcept C104317684 @default.
- W2001885803 hasConcept C12554922 @default.
- W2001885803 hasConcept C141315368 @default.
- W2001885803 hasConcept C143065580 @default.
- W2001885803 hasConcept C158617107 @default.
- W2001885803 hasConcept C17137333 @default.
- W2001885803 hasConcept C181199279 @default.
- W2001885803 hasConcept C185592680 @default.
- W2001885803 hasConcept C190062978 @default.
- W2001885803 hasConcept C23265538 @default.
- W2001885803 hasConcept C55493867 @default.
- W2001885803 hasConcept C86803240 @default.
- W2001885803 hasConceptScore W2001885803C104317684 @default.
- W2001885803 hasConceptScore W2001885803C12554922 @default.
- W2001885803 hasConceptScore W2001885803C141315368 @default.
- W2001885803 hasConceptScore W2001885803C143065580 @default.
- W2001885803 hasConceptScore W2001885803C158617107 @default.
- W2001885803 hasConceptScore W2001885803C17137333 @default.
- W2001885803 hasConceptScore W2001885803C181199279 @default.
- W2001885803 hasConceptScore W2001885803C185592680 @default.
- W2001885803 hasConceptScore W2001885803C190062978 @default.
- W2001885803 hasConceptScore W2001885803C23265538 @default.
- W2001885803 hasConceptScore W2001885803C55493867 @default.
- W2001885803 hasConceptScore W2001885803C86803240 @default.
- W2001885803 hasIssue "3" @default.
- W2001885803 hasLocation W20018858031 @default.
- W2001885803 hasOpenAccess W2001885803 @default.
- W2001885803 hasPrimaryLocation W20018858031 @default.
- W2001885803 hasRelatedWork W125884490 @default.
- W2001885803 hasRelatedWork W1488055363 @default.
- W2001885803 hasRelatedWork W1526761837 @default.
- W2001885803 hasRelatedWork W1571009912 @default.
- W2001885803 hasRelatedWork W1964461691 @default.
- W2001885803 hasRelatedWork W1988672938 @default.
- W2001885803 hasRelatedWork W1997731285 @default.
- W2001885803 hasRelatedWork W2069478194 @default.
- W2001885803 hasRelatedWork W2094393431 @default.
- W2001885803 hasRelatedWork W2463375115 @default.
- W2001885803 hasVolume "96" @default.
- W2001885803 isParatext "false" @default.
- W2001885803 isRetracted "false" @default.
- W2001885803 magId "2001885803" @default.
- W2001885803 workType "article" @default.