Abstract

Introduction

Materials & Methods

Results

Discussion & Conclusion

References

Discussion
Board

The SERCA ATPase is a 100,000 mw protein composed of a cytosolic globular region, connected through a stalk to a transmembrane region. This enzyme couples utilization of ATP to active transport of Ca2+ from the cytosol into membrane bound intracellular compartments ('Ca2+ stores'). The catalytic site, including the ATP binding domain and an aspartyl residue (Asp 351) which is phosphorylated as an intermediate step of ATP utilization, resides within the cytosolic globular region. Prior to ATP utilization, each enzyme molecule binds two Ca2+ (in exchange for H+) which are required for ATPase activation and are then transferred across the membrane as ATP is utilized. Mutational analysis indicates that the Ca2+ binding site resides within the transmembrane region. In fact, recent advances in recombinant enzyme production have permitted direct demonstration of Ca2+ binding defects following single site directed mutations on transmembrane helices. Similar experimentation suggests that the binding site for Thapsigargin (a highly specific inhibitor) is adjacent to the stalk (S3) segment. It is then apparent that the ATPase is an allosteric protein, and communication among catalytic, Ca2+ binding and Thapsigargin sites, occurs through long range intramolecular linkages.

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Presentation Number SAinesi0738
Keywords: calcium transport, SERCA ATPase, calcium stores, energy transduction, thapsigargin