Sarcolipin and phospholamban inhibit the calcium pump by populating a similar metal ion-free intermediate state.

ABSTRACT: We have performed microsecond molecular dynamics (MD) simulations and protein pKa calculations of the muscle calcium pump (sarcoplasmic reticulum Ca(2+)-ATPase, SERCA) in complex with sarcolipin (SLN) to determine the mechanism by which SLN inhibits SERCA. SLN and its close analog phospholamban (PLN) are membrane proteins that regulate SERCA by inhibiting Ca(2+) transport in skeletal and cardiac muscle. Although SLN and PLB binding to SERCA have different functional outcomes on the coupling efficiency of SERCA, both proteins decrease the apparent Ca(2+) affinity of the pump, suggesting that SLN and PLB inhibit SERCA by using a similar mechanism. Recently, MD simulations showed that PLB inhibits SERCA by populating a metal ion-free, partially-protonated E1 state of the pump, E1· [Formula: s

SUBMITTER: Espinoza-Fonseca LM 

PROVIDER: S-EPMC4465059 | biostudies-literature | 2015 Jul 17-24

REPOSITORIES: biostudies-literature