Abstract
P-type ATPases are membrane proteins acting as ion pumps that drive an active transport of cations across the membrane against a concentration gradient. The required energy for the ion transport is provided by binding and hydrolysis of ATP. A reaction mechanism of ion transport and energy transduction is assumed to be common for all P-type ATPases and generally described by the Post-Albers cycle. Transient currents and charge translocation of P-type ATPases were extensively investigated by electrical measurements that apply voltage jumps to initiate the reaction cycle. In this study, we simulate an applied voltage across the membrane by an electric field and perform electrostatic calculations in order to verify the experimentally-driven hypothesis that the energy transduction mechanism is regulated by specific structural elements. Side chain conformational and ionization changes induced by the electric field are evaluated for each transmembrane helix and the selectivity in response is qualitatively analyzed for the Ca2+-ATPase as well as for structural models of the Na+/K+-ATPase. Helix M5 responds with more conformer changes as compared to the other transmembrane helices what is even more emphasized when the stalk region is included. Thus our simulations support experimental results and indicate a crucial role for the highly conserved transmembrane helix M5 in the energy transduction mechanism of P-type ATPases.
Highlights
P-type ATPases are found in all branches of life and form a major class of ion pumps that are essential for many fundamental processes in biology [1]
The P-type ATPases use the energy of ATP that is bound and hydrolysed at the nucleotide binding domain located in the cytoplasmic part
In order to drive the active transport of cations through the transmembrane part, the energy provided at the cytoplasmic nucleotide binding site has to be transferred to the transmembrane domain where the ion transport takes place
Summary
P-type ATPases are found in all branches of life and form a major class of ion pumps that are essential for many fundamental processes in biology [1]. P-type ATPases are integral membrane proteins that share structural similarities as they contain a transmembrane region with α-helices that is connected to the cytoplasmic head part. In order to drive the active transport of cations through the transmembrane part, the energy provided at the cytoplasmic nucleotide binding site has to be transferred to the transmembrane domain where the ion transport takes place This basic reaction mechanism is shared by all P-type ATPases and is commonly described with the classical E1/E2 model (Post-Albers cycle) [3,4] with two main conformational enzyme states, E1 and E2. Selectivity in helix response to the electric field was studied by side chain conformational and ionization changes in order to analyze the role of the helix M5 in the energy transduction mechanism of P-type ATPases in general
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