P-type ATPases harness the energy of ATP to pump charged substrates across biological membranes. Mg2+ is required as a cofactor. ATPases in this group transport various molecules including heavy metals, phospholipids, K+, Ca2+, H+, Mg2+, Na+/K+, and H+/K+. P-type ATPases are made up of multiple structural domains. Only the catalytic domain, responsible for the hydrolysis of ATP, is part of the haloacid dehalogenase (HAD) superfamily. Because this domain performs the same reaction across the family, and does not appear to be responsible for the varying transport specificities of the enzymes, all p-type ATPases have been classified into a single family regardless of transport specificity.
Toyoshima, C., et al.
Crystal structure of the calcium pump of sarcoplasmic reticulum at 2.6 A resolution
▸ Abstract
Calcium ATPase is a member of the P-type ATPases that transport ions across the membrane against a concentration gradient. Here we have solved the crystal structure of the calcium ATPase of skeletal muscle sarcoplasmic reticulum (SERCA1a) at 2.6 A resolution with two calcium ions bound in the transmembrane domain, which comprises ten alpha-helices. The two calcium ions are located side by side and are surrounded by four transmembrane helices, two of which are unwound for efficient coordination geometry. The cytoplasmic region consists of three well separated domains, with the phosphorylation site in the central catalytic domain and the adenosine-binding site on another domain. The phosphorylation domain has the same fold as haloacid dehalogenase. Comparison with a low-resolution electron density map of the enzyme in the absence of calcium and with biochemical data suggests that large domain movements take place during active transport.
Evolution of substrate specificities in the P-type ATPase superfamily
▸ Abstract
P-type ATPases make up a large superfamily of ATP-driven pumps involved in the transmembrane transport of charged substrates. We have performed an analysis of conserved core sequences in 159 P-type ATPases. The various ATPases group together in five major branches according to substrate specificity, and not according to the evolutionary relationship of the parental species, indicating that invention of new substrate specificities is accompanied by abrupt changes in the rate of sequence evolution. A hitherto-unrecognized family of P-type ATPases has been identified that is expected to be represented in all the major phyla of eukarya.
