NMR studies of the interaction between human programmed cell death 5 and human p53.

Human programmed cell death 5 (PDCD5) is a protein playing a significant role in regulating both the apoptotic and paraptotic cell deaths. Resent findings show that PDCD5 is a positive regulator of Tip60 and also has a potential ability to interact with p53. Here we aim to experimentally characterize the nature of the interactions between PDCD5 and the p53 N-terminal domain (NTD) and to depict the binding mode between two proteins. The interprotein binding interfaces were determined by NMR experiments performed with PDCD5 and various fragments of p53 NTD. The binding affinity was investigated using the NMR titration experiments. Analysis revealed that the PDCD5 binding site on p53 is localized within residues 41-56 of p53 TAD2 subdomain while p53 binds preferentially to the positively charged surface region around the C-terminals of helices α3 and α5 and the N-terminal of helix α4 of PDCD5. The binding is mainly mediated through electrostatic interactions. The present data suggested a model for the interaction between PDCD5 and the p53 NTD.