title: The calcium binding sites in human annexin V by crystal structure analysis at 2.0 A resolution. Implications for membrane binding and calcium channel activity.
abstract: Crystal structure analysis and refinement at 2.0 A resolution of a rhombohedral crystal form of human annexin V at high calcium concentration revealed a domain motion compared to the previously analysed hexagonal crystal form. Five calcium ions were located on the convex face of the molecule. Three strongly bound calciums are liganded at protruding interhelical loops and Asp or Glu residues in homologous positions in repeats I, II and IV. Five proteinaceous oxygens and one solvent molecule form the coordination polyhedron in each case. The unoccupied seventh site is suggested as the phospholipid headgroup binding site. Two more weakly bound sites were identified by lanthanum labelling. The structural features suggest that annexin V attaches with its convex face to membranes by specific calcium mediated interactions with at least three phospholipids. The adjacent membrane bilayer may thus become locally disordered and permeable to allow calcium inflow through the central polar channel of the molecule.
authors: Max Planck Institut für Biochemie, Martinsried, FRG.
authors: R
authors: R
authors: Huber
authors: M
authors: M
authors: Schneider
authors: I
authors: I
authors: Mayr
authors: J
authors: J
authors: Römisch
authors: E P
authors: EP
authors: Paques
mesh_terms: D000595:Amino Acid Sequence; D017304:Annexin A5; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D003461:Crystallography; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011257:Pregnancy Proteins / Q000737:chemistry*; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D014961:X-Ray Diffraction
chemical_list: D017304:Annexin A5; D002135:Calcium-Binding Proteins; D011257:Pregnancy Proteins; D002118:Calcium