2XWR

Crystal structure of the DNA-binding domain of human p53 with extended N terminus

Summary for 2XWR

• Entry DOI: 10.2210/pdb2xwr/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 2YBG 3SAK
• Descriptor: CELLULAR TUMOR ANTIGEN P53, ZINC ION (3 entities in total)
• Functional Keywords: cell cycle, cancer, transcription factor, apoptosis
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 2
• Total formula weight: 46303.34

Authors

Joerger, A.C.,Natan, E.,Fersht, A.R. (deposition date: 2010-11-04, release date: 2011-03-30, Last modification date: 2024-05-08)

Primary citation

Natan, E.,Baloglu, C.,Pagel, K.,Freund, S.M.,Morgner, N.,Robinson, C.V.,Fersht, A.R.,Joerger, A.C.
Interaction of the P53 DNA-Binding Domain with its N-Terminal Extension Modulates the Stability of the P53 Tetramer.
J.Mol.Biol., 409:358-, 2011

PubMed Abstract: The tetrameric tumor suppressor p53 plays a pivotal role in the control of the cell cycle and provides a paradigm for an emerging class of oligomeric, multidomain proteins with structured and intrinsically disordered regions. Many of its biophysical and functional properties have been extrapolated from truncated variants, yet the exact structural and functional role of certain segments of the protein is unclear. We found from NMR and X-ray crystallography that the DNA-binding domain (DBD) of human p53, usually defined as residues 94-292, extends beyond these domain boundaries. Trp91, in the hinge region between the disordered proline-rich N-terminal domain and the DBD, folds back onto the latter and has a cation-π interaction with Arg174. These additional interactions increase the melting temperature of the DBD by up to 2 °C and inhibit aggregation of the p53 tetramer. They also modulate the dissociation of the p53 tetramer. The absence of the Trp91/Arg174 packing presumably allows nonnative DBD-DBD interactions that both nucleate aggregation and stabilize the interface. These data have important implications for studies of multidomain proteins in general, highlighting the fact that weak ordered-disordered domain interactions can modulate the properties of proteins of complex structure.

PubMed: 21457718
DOI: 10.1016/J.JMB.2011.03.047

Experimental method

X-RAY DIFFRACTION (1.68 Å)