title: What can be learned about the function of a single protein from its various X-ray structures: the example of the sarcoplasmic calcium pump.
abstract: Improvements in the handling of membrane proteins for crystallization, combined with better synchrotron sources for X-ray diffraction analysis, are leading to clarification of the structural details of an ever increasing number of membrane transporters and receptors. Here we describe how this development has resulted in the elucidation at atomic resolution of a large number of structures of the sarcoplasmic Ca(2+)-ATPase (SERCA1a) present in skeletal muscle. The structures corresponding to the various intermediary states have been obtained after stabilization with structural analogues of ATP and of metal fluorides as mimicks of inorganic phosphate. From these results it is possible, in accordance with previous biochemical and molecular biology data, to give a detailed structural description of both ATP hydrolysis and Ca(2+) transport through the membrane, to serve as the starting point for a fuller understanding of the pump mechanism and, in future studies, on the regulatory role of this ubiquitous intracellular Ca(2+)-ATPase in cellular Ca(2+) metabolism in normal and pathological conditions.
authors.affiliation: Centre for Membrane Pumps in Cells and Disease - PUMPKIN, Danish National Research Foundation, Copenhagen, Denmark. jvm@biophys.au.dk
authors.forename: Jesper Vuust
authors.initials: JV
authors.lastname: Møller
authors.forename: Claus
authors.initials: C
authors.lastname: Olesen
authors.forename: Anne-Marie Lund
authors.initials: AM
authors.lastname: Winther
authors.forename: Poul
authors.initials: P
authors.lastname: Nissen
mesh_terms: D001692:Biological Transport; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000737:chemistry* / Q000378:metabolism*; D005459:Fluorides / Q000378:metabolism; D008954:Models, Biological; D017433:Protein Structure, Secondary; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D014961:X-Ray Diffraction / Q000379:methods*
chemical_list: D000252:Calcium-Transporting ATPases; D005459:Fluorides; D002118:Calcium