Predicted structure for the calcium-dependent membrane-binding proteins p35, p36, and p32.

Abstract

A new family of proteins (annexins) that bind to membranes at micromolar free Ca2+ has been recognized. Its members include an EGF-receptor kinase substrate (p35), a retroviral tyrosine kinase substrate (p36), the liver protein endonexin (p32) and an electric ray protein, calelectrin. Each protein contains four sequence repeats with a further 2-fold internal homology. Using the predicted secondary structure and pattern of conserved hydrophobic residues in each repeat, we have built a three-dimensional model that is largely isostructural with the known molecular conformation of bovine intestinal calcium-binding protein. The final (energy-refined) model had a core formed from the conserved hydrophobic residues. It differed from ICaBP principally in the length of the two Ca2+-binding loops with only one loop being able to bind. The model suggests a mechanism for interaction of these new Ca2+-binding proteins with phospholipid bilayers.