Structural Biology of Cardiac Muscle Contraction and Relaxation: From Understanding to Control

Cardiac contraction and relaxation are regulated by conformational transitions of protein complexes that are responsible for calcium trafficking through cell membranes. Central to the muscle relaxation phase is a dynamic membrane protein complex formed by Ca2+-ATPase (SERCA) and phospholamban (PLN), which in humans is responsible for approximately 70% of the calcium re-uptake in the sarcoplasmic reticulum. PLN is regulated by protein kinase A (PKA), which upon adrenergic stimulation phosphorylates PLN at S16. Dysfunction in this regulatory mechanism causes severe pathophysiologies.

In the past few years, my group has focused on the elucidation of the structure-dynamics-function correlations for the SERCA/PLN and PKA/PLN complexes. I will illustrate how it is possible to harness this knowledge to design new PLN mutants that can be used in gene therapy to reverse heart failure.

For more information contact Dr. Bridgette Barry (404-385-6085).