Oligomerization domain

The polypeptide chain of p53 is divided in three domains, each with its own function (Figure 9.16). Like many other transcription factors, p53 has an N-terminal activation domain followed by a DNA-binding domain, while the C-terminal 100 residues form an oligomerization domain involved in the formation of the p53 tetramers. Mutants lacking the C-terminal domain do not form tetramers, but the monomeric mutant molecules retain their sequence-specific DNA-binding properties in vitro. 

Figure 9.17 Schematic diagram illustrating the tetrameric stmcture of the pS3 oligomerization domain. The four subunits have different colors. Each subunit has a simple structure comprising a p strand and an a helix joined by a one-residue turn. The tetramer is built up from a pair of dimers (yellow-blue and red-green). Within each dimer the p strands form a two-stranded antiparallel p sheet which provides most of the subunit interactions. The two dimers are held together by interactions between the four a helices, which are packed in a different way from a four-helix bundle. (Adapted from P.D. Jeffrey et al.. Science 267 1498-1502, 1995.)...

POU regions bind to DNA by two tandemly oriented helix-turn-helix motifs Much remains to be learnt about the function of homeodomains in vivo Understanding tumorigenic mutations The monomeric p53 polypeptide chain is divided in three domains The oligomerization domain forms tetramers The DNA-binding domain of p53 is an antiparallel P barrel... 

Pelletier, J. N., Campbell-Valois, F.-X., and Michnick, S. W. (1998). Oligomerization domain-directed reassembly of active dihydro folate reductase from rationally designed fragments. Proc. Natl. Acad. Sci. USA 95, 12141-12146. 

Pakkanen, O., Hamalainen, E. R., Kivirikko, K. I., and Myllyharju.J. (2003). Assembly of stable human type I and III collagen molecules from hydroxylated recombinant chains in the yeast Pichia pastoris. Effect of an engineered C-terminal oligomerization domain foldon./. Biol. Chem. 278, 32478-32483. 

Fig. 13.13. Domain structure of the retinoblastoma protein pRb. The phosphorylation sites (P) of pRb and the localization of the sequence sections necessary for interaction with viral oncoproteins and with the transcription factor E2F are shown. In addition, an oligomerization domain and a DNA binding domain can be identified.

Frank, S., Lustig, A., Schulthess, T., Engel, J., and Kammerer, R. A. (2000). A distinct seven-residue trigger sequence is indispensable for proper coiled-coil formation of the human macrophage scavenger receptor oligomerization domain./. Biol. Chem. 275, 11672-11677. 

Burkhard, P., Meier, M., and Lustig, A. (2000b). Design of a minimal protein oligomerization domain by a structural approach. Prot. Sci. 9, 2294—2301. 

McAlinden, A., Smith, T. A., Sandell, L. J., Ficheux, D., Parry, D. A. D., and Hulmes, D. J. S. (2003). Alpha-helical coiled coil oligomerization domains are almost ubiquitous in the collagen superfamily. J. Biol. Chem. 278, 42200 2207. 

Fig. 20. Structurally characterized retroviral Gag proteins, (a) Capsid protein, N-terminal part (Gamble et al., 1996) (b) capsid protein, C-terminal oligomerization domain (Gamble et al, 1997) (c) matrix protein (Hill et al, 1996) (d) nucleocapsid protein (De Guzman et al, 1998).

Fig. 3. Domain structure of the 303-amino acid-long P22 scaffolding protein as determined by mutational analysis. The N-terminal one-third of the protein is involved in posttranscriptional autoregulation of synthesis. An oligomerization domain, involved in dimerization and tetramerization, whose boundaries are not well defined is located in the central region of the protein. Mutations that ablate portal and minor protein incorporation are located in the region between residues 210 and 250, and the C-terminal region forms a tetratricopeptide-like fold that interacts with the coat protein.

McWhirter JR, Galasso DL, Wang JY. A coiled-coil oligomerization domain of Bcr is essential for the transforming function of Bcr-Abl oncoproteins. Mol Cell Biol 1993 13 7587-95. 

Pur" means adenosine or guanine, while "Pyr" means thymine or cytosine. Continuing with the structure of p53, amino acids 320-360 are used for maintaining the adhesion of the four p53 proteins to each other (Prives, 1994). This domain is also called the "oligomerization domain."... 

The STAT proteins have an N-terminal oligomerization domain, an SH3 and an SH3 domain, a DNA binding domain and a C-terminal transactivation domain. Dimerization is mediated by the phosphotyrosine residue and the SH2 domain. Highly resolved structural investigation show that the phosphotyrosine residue of one Stat protein binds to the SH2 domain of the partner and vice versa, so that the phospho-tyrosine-SH2 bonds function as a double clasp (structure in complex with DNA Becker et al., 1998). The binding to DNA is in the form of a dimer, with the Stat-DNA... 

Lomax, M.E., Barnes, D.M., Hupp, T.R., Picksley, S.M., Camplejohn, R.S., 1998. Characterization of p53 oligomerization domain mutations isolated from Li-Fraumeni and Li-Fraumeni like family members. Oncogene 17, 643-649. 

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