Table 1.

Key residues within the hydrophobic core of the oligomerization domain of human p53 and alignment with p53 and p53-like proteins from different species

Species	Hydrophobic core/critical side chains*
	328	330	332	338	340	341	344	348
Human p53/mammals†	F/Y*	L	I	F/Y‡	M	F	L	L
Xenopus laevis						I
Rainbow trout						L	F
Zebrafish			V		I	L
Human p73			V		I	L
Squid			V		I	L		M
Chicken			V			L	I
Clam			V			L	I
Human p51	L		V			L	I
Rat KET	L		V			L	I
Japanese fish		F	V		F	L	I

^*The side chains of these residues are those found to contribute most to the thermodynamic stability of human p53tet (30). They correspond very closely with the side chains involved in the hydrophobic core (Fig. 1). The side chain of Arg-337 was found also critical for p53tet stability. However, the effect appeared to be due mainly to the contribution of its hydrophobic part; the few natural substitutions found at this position (Lys in trout, Thr in humans p51, and Asn in human p73, clam and squid) may not affect these hydrophobic interactions. Amino acid residue numbering is for human p53. For all other proteins, only amino acids that differ from those of human/mammalian p53tet at the equivalent positions are indicated. 

^†See ref. 34 and the Internet address http://perso.curie.fr/Thierry.Soussi/for references. The “mammalian” sequence corresponds to that of the following species: human, african green monkey, rhesus monkey, dog, cat, hamster, chinese hamster, rat, mouse, sheep, and bovine. 

^‡At position 328, Tyr was found in human p73 and trout, whereas Phe was found in all other sequences; at position 338, Phe was found in all mammalian sequences except dog, bovine, and human p51, and Tyr was found in all other sequences. Molecular modeling suggested that replacement of Phe by Tyr at either position would not entail any alteration of the hydrophobic core of p53tet; the hydroxyl group of Tyr could be accommodated on the protein surface without disrupting any interaction.