"We purified the part of the calcium pump that interacts with calcium-activated calmodulin, and we managed to crystallise a protein complex. To our great surprise, we found that the calcium pump binds two calmodulin proteins, and not just one as always assumed," explains Dr Tidow.
Calcium pump with three-step regulation
The fact that two calmodulin proteins are involved in the regulation of the calcium pump activity means that the calcium pump has three steps. It is switched off when no calcium-activated calmodulin is bound, it pumps at medium speed when binding occurs at one calmodulin protein, and it pumps at full speed when both calmodulin proteins are bound.
"Calcium pumps need considerable energy to transport calcium out of the cell. It is therefore important that they are only activated when there is a need to remove calcium. With two calmodulin-binding domains in the calcium pump, the cell can adjust the transportation to be energy efficient, at the same time as being able to quickly reduce the number of calcium ions if the concentration approaches a toxic level," Dr Poulsen concludes.
Mathematics reveals biological function
The researchers also used mathematical network modelling to further identify whether the calcium pump works differently depending on whether it is activated by zero, one or two calmodulin proteins. This revealed another characteristic of calcium pump regulation of calcium in the cell.
"We could show that the cell only responded to incoming calcium when concentrations above carefully defined threshold values were found. This may be important for the way cells define their status in the circadian rhythm or during cell division, for example," concludes Dr Tidow.
|Contact: Press Officer Carl Hagman|
University of Copenhagen