2YBG

Structure of Lys120-acetylated p53 core domain

Summary for 2YBG

• Entry DOI: 10.2210/pdb2ybg/pdb
• Related: 1A1U 1AIE 1C26 1DT7 1GZH 1H26 1HS5 1JSP 1KZY 1MA3 1OLG 1OLH 1PES 1PET 1SAE 1SAF 1SAH 1SAJ 1SAK 1SAL 1TSR 1TUP 1UOL 1XQH 1YCQ 1YCR 1YCS 2AC0 2ADY 2AHI 2ATA 2B3G 2BIM 2BIN 2BIO 2BIP 2BIQ 2FEJ 2FOJ 2FOO 2GS0 2H1L 2J0Z 2J10 2J11 2J1W 2J1X 2J1Y 2J1Z 2J20 2J21 2VUK 2WGX 2X0U 2X0V 2X0W 2XWR 3SAK
• Descriptor: CELLULAR TUMOR ANTIGEN P53, ZINC ION (3 entities in total)
• Functional Keywords: cell cycle, tumor suppressor, cancer, lysine acetylation, apoptosis
• 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: 4
• Total formula weight: 90448.08

Authors

Arbely, E.,Allen, M.D.,Joerger, A.C.,Fersht, A.R. (deposition date: 2011-03-08, release date: 2011-05-04, Last modification date: 2024-11-20)

Primary citation

Arbely, E.,Natan, E.,Brandt, T.,Allen, M.D.,Veprintsev, D.B.,Robinson, C.V.,Chin, J.W.,Joerger, A.C.,Fersht, A.R.
Acetylation of Lysine 120 of P53 Endows DNA- Binding Specificity at Effective Physiological Salt Concentration.
Proc.Natl.Acad.Sci.USA, 108:8251-, 2011

PubMed Abstract: Lys120 in the DNA-binding domain (DBD) of p53 becomes acetylated in response to DNA damage. But, the role and effects of acetylation are obscure. We prepared p53 specifically acetylated at Lys120, AcK120p53, by in vivo incorporation of acetylated lysine to study biophysical and structural consequences of acetylation that may shed light on its biological role. Acetylation had no affect on the overall crystal structure of the DBD at 1.9-Å resolution, but significantly altered the effects of salt concentration on specificity of DNA binding. p53 binds DNA randomly in vitro at effective physiological salt concentration and does not bind specifically to DNA or distinguish among its different response elements until higher salt concentrations. But, on acetylation, AcK120p53 exhibited specific DNA binding and discriminated among response elements at effective physiological salt concentration. AcK120p53 and p53 had the highest affinity to the same DNA sequence, although acetylation reduced the importance of the consensus C and G at positions 4 and 7, respectively. Mass spectrometry of p53 and AcK120p53 DBDs bound to DNA showed they preferentially segregated into complexes that were either DNA(p53DBD)(4) or DNA(AcK120DBD)(4), indicating that the different DBDs prefer different quaternary structures. These results are consistent with electron microscopy observations that p53 binds to nonspecific DNA in different, relaxed, quaternary states from those bound to specific sequences. Evidence is accumulating that p53 can be sequestered by random DNA, and target search requires acetylation of Lys120 and/or interaction with other factors to impose specificity of binding via modulating changes in quaternary structure.

PubMed: 21525412
DOI: 10.1073/PNAS.1105028108

Experimental method

X-RAY DIFFRACTION (1.9 Å)