REFINED SOLUTION STRUCTURE OF THE OLIGOMERIZATION DOMAIN OF THE TUMOR-SUPPRESSOR P53

The NMR solution structure of the oligomerization domain of the tumour suppressor p53 (residues 319-360) has been refined. The structure com prises a dimer of dimers, oriented in an approximately orthogonal mann er. The present structure determination is based on 4,472 experimental NMR restraints which represents a three and half fold increase over o ur previous work in the number of NOE restraints at the tetramerizatio n interface. A comparison with the recently solved 1.7 Angstrom resolu tion X-ray structure shows that the structures are very similar and th at the average angular root-mean-square difference in the interhelical angles is about 1 degrees. The results of recent extensive mutagenesi s data and the possible effects of mutations which have been identifie d in human cancers are discussed in the light of the present structure .