3w5d | pdb_00003w5d

Crystal structure of the calcium pump in the E2+Pi state

spinqualitylabelsall models 3w5d, resolution 2.45Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3w5d is a 1 chain structure with sequence from Oryctolagus cuniculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: NA, PTY, SO4 NonStd Res: ACE Related: 3w5a, 3w5b, 3w5c Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed P-type ATPases are ATP-powered ion pumps that establish ion concentration gradients across biological membranes, and are distinct from other ATPases in that the reaction cycle includes an autophosphorylation step. The best studied is Ca(2+)-ATPase from muscle sarcoplasmic reticulum (SERCA1a), a Ca(2+) pump that relaxes muscle cells after contraction, and crystal structures have been determined for most of the reaction intermediates. An important outstanding structure is that of the E1 intermediate, which has empty high-affinity Ca(2+)-binding sites ready to accept new cytosolic Ca(2+). In the absence of Ca(2+) and at pH 7 or higher, the ATPase is predominantly in E1, not in E2 (low affinity for Ca(2+)), and if millimolar Mg(2+) is present, one Mg(2+) is expected to occupy one of the Ca(2+)-binding sites with a millimolar dissociation constant. This Mg(2+) accelerates the reaction cycle, not permitting phosphorylation without Ca(2+) binding. Here we describe the crystal structure of native SERCA1a (from rabbit) in this E1.Mg(2+) state at 3.0 A resolution in addition to crystal structures of SERCA1a in E2 free from exogenous inhibitors, and address the structural basis of the activation signal for phosphoryl transfer. Unexpectedly, sarcolipin, a small regulatory membrane protein of Ca(2+)-ATPase, is bound, stabilizing the E1.Mg(2+) state. Sarcolipin is a close homologue of phospholamban, which is a critical mediator of beta-adrenergic signal in Ca(2+) regulation in heart (for reviews, see, for example, refs 8-10), and seems to play an important role in muscle-based thermogenesis. We also determined the crystal structure of recombinant SERCA1a devoid of sarcolipin, and describe the structural basis of inhibition by sarcolipin/phospholamban. Thus, the crystal structures reported here fill a gap in the structural elucidation of the reaction cycle and provide a solid basis for understanding the physiological regulation of the calcium pump. Crystal structures of the calcium pump and sarcolipin in the Mg2+-bound E1 state.,Toyoshima C, Iwasawa S, Ogawa H, Hirata A, Tsueda J, Inesi G Nature. 2013 Mar 14;495(7440):260-4. doi: 10.1038/nature11899. Epub 2013 Mar 3. PMID:23455422 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also ATPase

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