The N-terminal domain of MDM2 resembles calmodulin and its relatives

It is shown here that the N-terminal domain of MDM2, which is not thought to bind calcium ions, otherwise bears a striking resemblance to a cluster of four EF-hand modules like those found in the calmodulin family. There are similarities in module arrangement, supersecondary structure and the main-chain to main-chain hydrogen-bonding pattern, especially in the vicinity of the short antiparallel beta-sheet, the two strands of which lie between the two E and F helices of tandem modules. Some conserved amino acid residues are identified that are associated with short side-chain to main-chain hydrogen-bonded motifs. Also, both types of domain bind a short, functionally important hydrophobic alpha-helix from another protein in a cavity between the two pairs of EF-hand, or EF-hand-like, modules. (C) 1999 Academic Press.