1HS5

NMR SOLUTION STRUCTURE OF DESIGNED P53 DIMER

Summary for 1HS5

• Entry DOI: 10.2210/pdb1hs5/pdb
• Descriptor: CELLULAR TUMOR ANTIGEN P53 (1 entity in total)
• Functional Keywords: dimer, anti-parallel beta-turn-helix, gene regulation
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm. Isoform 1: Nucleus. Isoform 2: Nucleus. Isoform 3: Nucleus. Isoform 4: Nucleus. Isoform 7: Nucleus. Isoform 8: Nucleus. Isoform 9: Cytoplasm: P04637
• Total number of polymer chains: 2
• Total formula weight: 8217.02

Authors

Davison, T.S.,Nie, X.,Ma, W.,Li, Y.,Kay, C.,Benchimol, S.,Arrowsmith, C.H. (deposition date: 2000-12-22, release date: 2001-01-10, Last modification date: 2024-05-22)

Primary citation

Davison, T.S.,Nie, X.,Ma, W.,Lin, Y.,Kay, C.,Benchimol, S.,Arrowsmith, C.H.
Structure and functionality of a designed p53 dimer.
J.Mol.Biol., 307:605-617, 2001

PubMed Abstract: P53 is a homotetrameric tumor suppressor protein involved in transcriptional control of genes that regulate cell proliferation and death. In order to probe the role that oligomerization plays in this capacity, we have previously designed and characterized a series of p53 proteins with altered oligomeric states through hydrophilc substitution of residues Met340 or Leu344 in the normally tetrameric oligomerization domain. Although such mutations have little effect on the overall secondary structural content of the oligomerization domain, both solubility and the resistance to thermal denaturation are substantially reduced relative to that of the wild-type domain. Here, we report the design and characterization of a double-mutant p53 with alterations of residues at positions Met340 and Leu344. The double-mutations Met340Glu/Leu344Lys and Met340Gln/Leu344Arg resulted in distinct dimeric forms of the protein. Furthermore, we have verified by NMR structure determination that the double-mutant Met340Gln/Leu344Arg is essentially a "half-tetramer". Analysis of the in vivo activities of full-length p53 oligomeric mutants reveals that while cell-cycle arrest requires tetrameric p53, transcriptional transactivation activity of monomers and dimers retain roughly background and half of the wild-type activity, respectively.

PubMed: 11254385
DOI: 10.1006/jmbi.2001.4450

Experimental method

SOLUTION NMR