Details

Autor(en) / Beteiligte

• Møller, Jesper Vuust
• Gyrup, Claus
• Picard, Martin
• Nissen, Poul
• Olesen, Claus
• Winther, Anne-Marie Lund
• Morth, J. Preben
• Oxvig, Claus

Titel

The structural basis of calcium transport by the calcium pump

Ist Teil von

• Nature, 2007-12, Vol.450 (7172), p.1036-1042

Ort / Verlag

London: Nature Publishing

Erscheinungsjahr

2007

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• The sarcoplasmic reticulum Ca2+-ATPase, a P-type ATPase, has a critical role in muscle function and metabolism. Here we present functional studies and three new crystal structures of the rabbit skeletal muscle Ca2+-ATPase, representing the phosphoenzyme intermediates associated with Ca2+ binding, Ca2+ translocation and dephosphorylation, that are based on complexes with a functional ATP analogue, beryllium fluoride and aluminium fluoride, respectively. The structures complete the cycle of nucleotide binding and cation transport of Ca2+-ATPase. Phosphorylation of the enzyme triggers the onset of a conformational change that leads to the opening of a luminal exit pathway defined by the transmembrane segments M1 through M6, which represent the canonical membrane domain of P-type pumps. Ca2+ release is promoted by translocation of the M4 helix, exposing Glu 309, Glu 771 and Asn 796 to the lumen. The mechanism explains how P-type ATPases are able to form the steep electrochemical gradients required for key functions in eukaryotic cells.