Tuning the structural coupling between the transmembrane and cytoplasmic domains of phospholamban to control sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) function.

ABSTRACT: Phospholamban (PLN) is the endogenous inhibitor of the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA), the integral membrane enzyme responsible for 70 % of the removal of Ca(2+) from the cytosol, inducing cardiac muscle relaxation in humans. Dysfunctions in SERCA:PLN interactions have been implicated as having a critical role in cardiac disease, and targeting Ca(2+) transport has been demonstrated to be a promising avenue in treating conditions of heart failure. Here, we designed a series of new mutants able to tune SERCA function, targeting the loop sequence that connects the transmembrane and cytoplasmic helices of PLN. We found that a variable degree of loss of inhibition mutants is attainable by engineering glycine mutations along PLN's loop domain. Remarkably, a double glycine mut

SUBMITTER: Ha KN 

PROVIDER: S-EPMC3522752 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature