PDBsum entry: 1cok

Gene regulation

PDB id: 1cok

Contents

Protein chain

68 a.a. *

* Residue conservation analysis

PDB id:

1cok

Name:

Gene regulation

Title:

Structure of thE C-terminal domain of p73

Structure:

Protein (second splice variant p73). Chain: a. Fragment: c-terminal domain. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Variant: p73alpha. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

NMR struc:

18 models

Authors:

S.-W.Chi,A.Ayed,C.H.Arrowsmith

Key ref:

S.W.Chi et al. (1999). Solution structure of a conserved C-terminal domain of p73 with structural homology to the SAM domain. EMBO J, 18, 4438-4445. PubMed id: 10449409 DOI: 10.1093/emboj/18.16.4438

Date:

28-May-99 Release date: 17-Aug-99

Protein chain

O15350  (P73_HUMAN) -  Tumor protein p73

Seq: 636 a.a.

Struc: 68 a.a.

DOI no: 10.1093/emboj/18.16.4438

EMBO J 18:4438-4445 (1999)

PubMed id: 10449409

Solution structure of a conserved C-terminal domain of p73 with structural homology to the SAM domain.

S.W.Chi, A.Ayed, C.H.Arrowsmith.

ABSTRACT

p73 and p63 are two recently cloned genes with homology to the tumor suppressor p53, whose protein product is a key transcriptional regulator of genes involved in cell cycle arrest and apoptosis. While all three proteins share conserved transcriptional activation, DNA-binding and oligomerization domains, p73 and p63 have an additional conserved C-terminal region. We have determined the three-dimensional solution structure of this conserved C-terminal domain of human p73. The structure reveals a small five-helix bundle with striking similarity to the SAM (sterile alpha motif) domains of two ephrin receptor tyrosine kinases. The SAM domain is a putative protein-protein interaction domain found in a variety of cytoplasmic signaling proteins and has been shown to form both homo- and hetero-oligomers. However, the SAM-like C-terminal domains of p73 and p63 are monomeric and do not interact with one another, suggesting that this domain may interact with additional, as yet uncharacterized proteins in a signaling and/or regulatory role.

Selected figure(s)

Figure 3.
Figure 3 A backbone representation of the solution structure residues 491–550 of p73. Residues 487–490 and 551–554 are unstructured and are not displayed. (A) The superposition of the 18 lowest energy structures. Helices 1–5 are colored yellow, green, cyan, pink and red, respectively. (B) A ribbon display of a representative structure. The side chains are displayed for conserved hydrophobic residues involved in the association of the five helices: L497 (yellow); L500 (white); I506, F509 (green); L514 (white); L520 (blue); L528 (pink); and I541, W542, L545 (red). Each of these residues corresponds to a hydrophonic or aliphatic residue in the SAM domain consensus sequence derived by Shultz et al. (1997). Graphics were generated with InstightII. The atomic coordinates have been deposited in the Protein Data Bank, accession number 1cok.

Figure 5.
Figure 5 Representative sedimentation equilibrium data, fitted curves and residuals for p73 C-terminal proteins. (A) p73(487–554) (0.2 mg/ml, 22 500 r.p.m.). The apparent molecular weight obtained from the fitting procedure was 9395 Da (expected molecular weight for the mononer is 10 096 Da). (B) p73(487–600) (0.5 mg/ml, 35 000 r.p.m.). The apparent molecular weight obtained from the fitting procedure was 13 922 Da (expected molecular weight for the monomer is 15 124 Da).

The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (1999, 18, 4438-4445) copyright 1999.

Figures were selected by an automated process.