- P73 is a transcription factor of the p53 protein family. It has a number of roles including control of apoptosis, cell cycle regulation and the nervous system
- The DBD is composed of 3 α-helices, 10 β-strands and 3 loops. The β-strands form a β-sandwich
- In the absence of DNA, the p73 DBD is a monomer. Upon DNA binding, it dimerises, and two adjacent dimers form a tetramer
- The p73 DBD binds a response element. Two half sites make up the response element, and these can be separated by a 0, 1, 2 or 4bp spacer
- A p73 dimer recognises a half site within the RE, but only binds a quarter site
- The key DBD residues which interact with the bases of the response element are Arg300, Cys297 and Lys138
- The key DBD residues which interact with the phosphates on the DNA backbone are Lys138, Ala296, Ser261, Arg268 and Arg293
- Intermolecular interactions within the DBD tetramer include monomer-monomer interactions and dimer-dimer interactions
- Two distinct dimer conformations exist, one dependent on tetramerisation and the other not
- As spacer length increases, distance between the tetramerisation interfaces increases, causing a change in tetramer conformation
- The conformation of the response element DNA adapts in order to allow for tetramerisation
- p73 is homologous to p53. p73 has 20 to 100 times less affinity for DNA than p53, because the p73 dimer-dimer interface has fewer interactions
- For each increase in spacer length, the transactivational activity of p73 significantly declines
I really like the pymol diagrams, they look really good. There is quite a lot of text, but its written well, so its still easy to read.
ReplyDeleteNice work!