| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1931304 | Biochemical and Biophysical Research Communications | 2010 | 6 Pages |
The association between the cardiac transmembrane proteins phospholamban and sarcoplasmic reticulum Ca2+ ATPase (SERCA2a) regulates the active transport of Ca2+ into the sarcoplasmic reticulum (SR) lumen and controls the contraction and relaxation of the heart. Heart failure (HF) and cardiac hypertrophy have been linked to defects in Ca2+ uptake by the cardiac SR and stimulation of calcium transport by modulation of the PLB-SERCA interaction is a potential therapy. This work is part of an effort to identify compounds that destabilise the PLB-SERCA interaction in well-defined membrane environments. It is shown that heparin-derived oligosaccharides (HDOs) interact with the cytoplasmic domain of PLB and consequently stimulate SERCA activity. These results indicate that the cytoplasmic domain of PLB is functionally important and could be a valid target for compounds with drug-like properties.
Research highlights► The phospholamban cytoplasmic domain lowers the rate of ATP hydrolysis by SERCA. ► Heparin-derived oligosaccharides interact with the phospholamban cytoplasmic domain. ► The interaction reverses the effect of phospholamban on SERCA function in phospholipid membranes. ► The phospholamban cytoplasmic domain is a potential drug target for heart failure.
