1. Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan
2. The Harima Institute, The Institute of Physical and Chemical Research, Sayo-gun, Hyo-go 679-5143, Japan
3. PRESTO, Japan Science and Technology Corporation, Kawaguchi 332-0012, Japan

Correspondence to: Chikashi Toyoshima^1,2 Correspondence and requests for materials should be addressed to C.T. (e-mail: Email: ct@iam.u-tokyo.ac.jp). The atomic coordinates have been deposited in the PDB (accession code 1EUL).

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 Å resolution with two calcium ions bound in the transmembrane domain, which comprises ten -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.