HIGH-RESOLUTION STRUCTURE OF THE OLIGOMERIZATION DOMAIN OF P53 BY MULTIDIMENSIONAL NMR

The three-dimensional structure of the oligomerization domain (residue s 319 to 360) of the tumor suppressor p53 has been solved by multidime nsional heteronuclear magnetic resonance (NMR) spectroscopy. The domai n forms a 20-kilodalton symmetric tetramer with a topology made up fro m a dimer of dimers. The two primary dimers each comprise two antipara llel helices linked by an antiparallel beta sheet. One beta strand and one helix are contributed from each monomer. The interface between th e two dimers forming the tetramer is mediated solely by helix-helix co ntacts. The overall result is a symmetric, four-helix bundle with adja cent helices oriented antiparallel to each other and with the two anti parallel beta sheets located on opposing faces of the molecule. The te tramer is stabilized not only by hydrophobic interactions within the p rotein core but also by a number of electrostatic interactions. The im plications of the structure of the tetramer for the biological functio n of p53 are discussed.