Structure of the C-terminal sterile α-motif (SAM) domain of human p73α

p73 is a homologue of the tumour suppressor p53 and contains all three functional domains of p53. The α-splice variant of p73 (p73α) contains near its C-terminus an additional structural domain known as the sterile α-motif (SAM) that is probably responsible for regulating p53-like functions of p73. Here, the 2.54 Å resolution crystal structure of this protein domain is reported. The crystal structure and the published solution structure have the same five-helix bundle fold that is characteristic of all SAM-domain structures, with an overall r.m.s.d. of 1.5 Å for main-chain atoms. The hydrophobic core residues are well conserved, yet some large local differences are observed. The crystal structure reveals a dimeric organization, with the interface residues forming a mini four-helix bundle. However, analysis of solvation free energies and the surface area buried upon dimer formation indicated that this arrangement is more likely to be an effect of crystal packing rather than reflecting a physiological state. This is consistent with the solution structure being a monomer. The p73α SAM domain also contains several interesting structural features: a Cys-X-X-Cys motif, a 3₁₀-helix and a loop that have elevated B factors, and short tight inter-helical loops including two β-turns; these elements are probably important in the normal function of this domain.