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Updated: Aug 14, 2026

Controlling the Size, Shape and Stability of Supramolecular Polymers in Water
Published on: August 2, 2012
Hydrophobic side-chain size is a determinant of the three-dimensional structure of the p53 oligomerization domain
M McCoy1, E S Stavridi, J L Waterman
1Departments of Molecular Genetics and Structural Biology, The Wistar Institute, Philadelphia, PA 19104-4268, USA.
Abstract:
The p53 tumor suppressor oligomerization domain, a dimer of two primary dimers, is an independently folding domain whose subunits consist of a beta-strand, a tight turn and an alpha-helix. To evaluate the effect of hydrophobic side-chains on three-dimensional structure, we substituted residues Phe341 and Leu344 in the alpha-helix with other hydrophobic amino acids. Substitutions that resulted in residue 341 having a smaller side-chain than residue 344 switched the stoichiometry of the domain from tetrameric to dimeric. The three-dimensional structure of one such dimer was determined by multidimensional NMR spectroscopy. When compared with the primary dimer of the wild-type p53 oligomerization domain, the mutant dimer showed a switch in alpha-helical packing from anti-parallel to parallel and rotation of the alpha-helices relative to the beta-strands. Hydrophobic side-chain size is therefore an important determinant of a protein fold.
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