Turbo switch uncovered in calcium pump

Using the X-ray source DORIS and the European Synchrotron Radiation Facility ESRF, scientists discovered that the on-off switch of the pump has a previously unknown third position, which switches the pump into a turbo gear.

“The discovery not only improves our understanding of a fundamental mechanism in the biology of all higher organisms, but could one day allow for better treatment of certain diseases in which the calcium balance is disturbed,” said researcher Henning Tidow.

The calcium pump maintains the calcium concentration within a cell using a “switch” which is activated by the protein calmodulin.

When calcium binds to calmodulin, the latter changes its shape so that it can dock onto a binding site of the cell’s calcium pump, thereby activating the pump.

The researchers led by Tidow viewed the entire switching complex with X-rays to reveal its molecular structure.

They chose the switching complex from cells of the plant thale cress (Arabidopsis thaliana), studying it first in crystal form and then in solution, which is closer to the natural environment of the molecule.

“Our results show that the calcium pump is controlled in three steps,” said Poulsen. “It is switched off when no calmodulin is bound to the switching complex. The pump is running at medium speed as soon as one binding site is occupied, and at full speed when calmodulin is bound to both sites.”

The pump is activated step by step, depending on how much calcium is present in the cell.

When the calcium concentration increases, the pump first operates in an energy-efficient way at moderate speed.

If the calcium threatens to reach an amount that is dangerous for the cell, the pump changes into the turbo gear, which enables it to very quickly reduce the concentration.

Bioinformatics analyses revealed that this double switch occurs not only in all plant species, but in general in all cells with a nucleus.

“This study underscores the strength of integrating structural biology in interdisciplinary research,” underlines Poul Nissen of Aarhus University.

As the next step, the researchers aim to decipher the structure of the entire calcium pump.