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

• Published in: FEBS letters 1990-11, Vol.275 (1), p.15-21
• Main Authors: Huber, Robert, Schneider, Monika, Mayr, Irmgard, Römisch, Jürgen, Paques, Eric-P.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Annexin; Annexin A5; Binding Sites; Biological and medical sciences; Calcium; Calcium - metabolism; Calcium-Binding Proteins - chemistry; Calcium-Binding Proteins - metabolism; Cell Membrane - metabolism; Channel; Crystal structure; Crystalline structure; Crystallography; Fundamental and applied biological sciences. Psychology; Humans; Membrane; Models, Molecular; Molecular biophysics; Molecular Sequence Data; Pregnancy Proteins - chemistry; Protein Conformation; Structure in molecular biology; Structure-Activity Relationship; X-Ray Diffraction
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(90)81428-Q

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 specified 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.