Structural basis for allosteric control of the SERCA-Phospholamban membrane complex by Ca²⁺ and phosphorylation.

ABSTRACT: Phospholamban (PLN) is a mini-membrane protein that directly controls the cardiac Ca²⁺-transport response to β-adrenergic stimulation, thus modulating cardiac output during the fight-or-flight response. In the sarcoplasmic reticulum membrane, PLN binds to the sarco(endo)plasmic reticulum Ca²⁺-ATPase (SERCA), keeping this enzyme's function within a narrow physiological window. PLN phosphorylation by cAMP-dependent protein kinase A or increase in Ca²⁺ concentration reverses the inhibitory effects through an unknown mechanism. Using oriented-sample solid-state NMR spectroscopy and replica-averaged NMR-restrained structural refinement, we reveal that phosphorylation of PLN's cytoplasmic regulatory domain signals the disruption of several inhibitory contacts at

SUBMITTER: Weber DK 

PROVIDER: S-EPMC8184213 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature