Aarhus University Seal / Aarhus Universitets segl

P1-, P3- & P5-ATPases: Structure, function and regulation

Group leader: prof. Michael Broberg Palmgren

We study the structure, function and regulation of P-type pumps. All members of this family of ubiquitous transporters form a phosphorylated reaction cycle intermediate. Some, like proton pumping P3 ATPases, energize the membranes of cells and play essential roles in cellular cation homeostasis, others, like P4 and P5 ATPases, are still poorly characterized even though they are very abundant.

So far, my group identified the regulatory domain of the plant plasma membrane proton pump and has identified several regulatory proteins and compounds acting via this platform. In order to understand the mechanism of the plasma membrane proton pump, we developed an efficient heterologous expression system to study it, a system that has proven useful for the characterization of other P-type pumps. We identified the ion binding sites of the proton pump, and in collaboration with Poul Nissen, Aarhus Univ., were first to obtain a crystal structure of this pump. We were the first to clone a plant plasma membrane Ca2+-ATPase and subsequently identified the unique N-terminal regulatory domain of this pump and recently in collaboration with the Nissen lab characterized the crystal structure of this domain in complex with calmodulin. We were first to elucidate the phylogenetic relationships between P-type ATPases, gave name to the families in the current classification system, and pointed to the presence of P4 and P5 pumps. Further, we were the first to identify and characterize plant P4 ATPases and their b-subunits (putative lipid flippases) and the first laboratory to identify and characterize plant P5 ATPases (putative secretory pathway pumps).

Presently, focus in our laboratory is on the characterization of the transport mecanism of proton pumping of P3 ATPases, identification of the transported ligand(s) and physiological role of orphan pumps (P5 ATPases), the role of Zn pumping P1B ATPases in plant physiology, and epigenetic mechanisms regulating expression in plants of P-type ATPases.

Recent publications:

Tidow H, Poulsen LR, Andreeva A, Knudsen M, Hein KL, Wiuf C, Palmgren MG, Nissen P (2012) A bimodular mechanism of calcium control in eukaryotes. Nature 491:468-472.

Mikkelsen MD, Pedas P, Schiller M, Vincze E, Mills RF, Borg S, Møller A, Schjoerring JK, Williams LE, Baekgaard L, Holm PB, Palmgren MG (2012) Barley HvHMA1 is a heavy metal pump involved in mobilizing organellar Zn and Cu and plays a role in metal loading into grains. PLoS One 7(11):e49027

Sørensen DM, Møller AB, Jakobsen MK, Jensen MK, Vangheluwe P, Buch-Pedersen MJ, Palmgren MG (2012) Ca2+ induces spontaneous dephosphorylation of a novel P5A-type ATPase. J Biol Chem 287: 28336-48.

Pedersen CN, Axelsen KB, Harper JF, Palmgren MG (2012) Evolution of plant p-type ATPases. Front Plant Sci 3: 31.

López-Marqués RL, Poulsen LR, Palmgren MG (2012) A putative plant aminophospholipid flippase, the Arabidopsis P4 ATPase ALA1, localizes to the plasma membrane following association with a β-subunit. PLoS One 7: e33042.

Rudashevskaya EL, Ye J, Jensen ON, Fuglsang AT, Palmgren MG (2012) Phosphosite mapping of P-type plasma membrane H+-ATPase in homologous and heterologous environments. J Biol Chem 287: 4904-13.