title: Calcium binding studies of peptides of human phospholipid scramblases 1 to 4 suggest that scramblases are new class of calcium binding proteins in the cell.
abstract: BACKGROUND
  Phospholipid scramblases are a group of four homologous proteins conserved from C. elegans to human. In human, two members of the scramblase family, hPLSCR1 and hPLSCR3 are known to bring about Ca2+ dependent translocation of phosphatidylserine and cardiolipin respectively during apoptotic processes. However, affinities of Ca2+/Mg2+ binding to human scramblases and conformational changes taking place in them remains unknown.
  
  
  METHODS
  In the present study, we analyzed the Ca2+ and Mg2+ binding to the calcium binding motifs of hPLSCR1-4 and hPLSCR1 by spectroscopic methods and isothermal titration calorimetry.
  
  
  RESULTS
  The results in this study show that (i) affinities of the peptides are in the order hPLSCR1>hPLSCR3>hPLSCR2>hPLSCR4 for Ca2+ and in the order hPLSCR1>hPLSCR2>hPLSCR3>hPLSCR4 for Mg2+, (ii) binding of ions brings about conformational change in the secondary structure of the peptides. The affinity of Ca2+ and Mg2+ binding to protein hPLSCR1 was similar to that of the peptide I. A sequence comparison shows the existence of scramblase-like motifs among other protein families.
  
  
  CONCLUSIONS
  Based on the above results, we hypothesize that the Ca2+ binding motif of hPLSCR1 is a novel type of Ca2+ binding motif.
  
  
  CONCLUSIONS
  Our findings will be relevant in understanding the calcium dependent scrambling activity of hPLSCRs and their biological function.
authors.affiliation: Department of Biotechnology, Indian Institute of Technology--Madras, Chennai 600 036, India.
authors.forename: Santosh Kumar
authors.initials: SK
authors.lastname: Sahu
authors.forename: Gopala Krishna
authors.initials: GK
authors.lastname: Aradhyam
authors.forename: Sathyanarayana N
authors.initials: SN
authors.lastname: Gummadi
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D001667:Binding, Competitive; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002942:Circular Dichroism; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D008274:Magnesium / Q000378:metabolism; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D049294:Phospholipid Transfer Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D013725:Terbium / Q000737:chemistry / Q000378:metabolism; D014364:Tryptophan / Q000737:chemistry / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; C493422:PLSCR1 protein, human; C493423:PLSCR2 protein, human; C493424:PLSCR3 protein, human; C493425:PLSCR4 protein, human; D010455:Peptides; D049294:Phospholipid Transfer Proteins; D013725:Terbium; D014364:Tryptophan; D008274:Magnesium; D002118:Calcium