%0 Journal Article %1 mccoy_hydrophobic_1997 %A McCoy, M %A Stavridi, E S %A Waterman, J L %A Wieczorek, A M %A Opella, S J %A Halazonetis, T D %D 1997 %J EMBO J. %K Acid Amino Binding,Protein Data,Mutation,Peptide Fragments,Protein Protein Resonance Sequence Sequence,Dimerization,Magnetic Spectroscopy,Models,Molecular,Molecular Structure,Secondary,Tumor Suppressor p53 %N 20 %P 6230--6236 %R 10.1093/emboj/16.20.6230 %T Hydrophobic side-chain size is a determinant of the three-dimensional structure of the p53 oligomerization domain %V 16 %X 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.

@article{mccoy_hydrophobic_1997, 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.}, added-at = {2017-03-14T02:48:56.000+0100}, author = {McCoy, M and Stavridi, E S and Waterman, J L and Wieczorek, A M and Opella, S J and Halazonetis, T D}, biburl = {https://www.bibsonomy.org/bibtex/2f1fcff6347705959cacfe5fe23caf5bd/nmrresource}, doi = {10.1093/emboj/16.20.6230}, interhash = {0b22979c19240bc42176566c5ea6f014}, intrahash = {f1fcff6347705959cacfe5fe23caf5bd}, issn = {0261-4189}, journal = {EMBO J.}, keywords = {Acid Amino Binding,Protein Data,Mutation,Peptide Fragments,Protein Protein Resonance Sequence Sequence,Dimerization,Magnetic Spectroscopy,Models,Molecular,Molecular Structure,Secondary,Tumor Suppressor p53}, month = oct, number = 20, pages = {6230--6236}, pmid = {9321402}, timestamp = {2017-03-14T02:49:21.000+0100}, title = {{Hydrophobic side-chain size is a determinant of the three-dimensional structure of the p53 oligomerization domain}}, volume = 16, year = 1997 }