TY - JOUR
T1 - Structural identification of cation binding pockets in the plasma membrane proton pump
AU - Ekberg, Kira
AU - Pedersen, Bjørn Panella
AU - Sørensen, Danny Mollerup
AU - Nielsen, Ann Kallehauge
AU - Veierskov, Bjarke
AU - Nissen, Poul
AU - Palmgren, Michael Broberg
AU - Buch-Pedersen, Morten Jeppe
PY - 2010/12/14
Y1 - 2010/12/14
N2 - The activity of P-type plasma membrane H+-ATPases is modulated by H+ and cations, with K+ and Ca2+ being of physiological relevance. Using X-ray crystallography, we have located the binding site for Rb+ as a K+ congener, and for Tb 3+ and Ho3+ as Ca2+ congeners. Rb+ is found coordinated by a conserved aspartate residue in the phosphorylation domain. A single Tb3+ ion is identified positioned in the nucleotide-binding domain in close vicinity to the bound nucleotide. Ho 3+ ions are coordinated at two distinct sites within the H +-ATPase: One site is at the interface of the nucleotidebinding and phosphorylation domains, and the other is in the transmembrane domain toward the extracellular side. The identified binding sites are suggested to represent binding pockets for regulatory cations and a H+ binding site for protons leaving the pump molecule. This implicates Ho3+ as a novel chemical tool for identification of proton binding sites.
AB - The activity of P-type plasma membrane H+-ATPases is modulated by H+ and cations, with K+ and Ca2+ being of physiological relevance. Using X-ray crystallography, we have located the binding site for Rb+ as a K+ congener, and for Tb 3+ and Ho3+ as Ca2+ congeners. Rb+ is found coordinated by a conserved aspartate residue in the phosphorylation domain. A single Tb3+ ion is identified positioned in the nucleotide-binding domain in close vicinity to the bound nucleotide. Ho 3+ ions are coordinated at two distinct sites within the H +-ATPase: One site is at the interface of the nucleotidebinding and phosphorylation domains, and the other is in the transmembrane domain toward the extracellular side. The identified binding sites are suggested to represent binding pockets for regulatory cations and a H+ binding site for protons leaving the pump molecule. This implicates Ho3+ as a novel chemical tool for identification of proton binding sites.
U2 - 10.1073/pnas.1010416107
DO - 10.1073/pnas.1010416107
M3 - Journal article
C2 - 21098259
SN - 0027-8424
VL - 107
SP - 21400
EP - 21405
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 50
ER -