Hydrophobic side-chain size is a determinant of the three-dimensional structure of the p53 oligomerization domain

被引:41
作者
McCoy, M
Stavridi, ES
Waterman, JLF
Wieczorek, AM
Opella, SJ
Halazonetis, TD
机构
[1] WISTAR INST ANAT & BIOL,DEPT MOL GENET,PHILADELPHIA,PA 19104
[2] WISTAR INST ANAT & BIOL,DEPT BIOL STRUCT,PHILADELPHIA,PA 19104
[3] UNIV PENN,DEPT CHEM,PHILADELPHIA,PA 19104
[4] UNIV PENN,DEPT PATHOL & LAB MED,PHILADELPHIA,PA 19104
关键词
hydrophobic effect; NMR spectroscopy; p53 tumor suppressor; protein design; protein structure;
D O I
10.1093/emboj/16.20.6230
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 tig ht turn anti an alpha-helix. To evaluate the effect of hydrophobic side-chains on three-dimensional structure, we substituted residues Phe341 and Leu344 in the a-helix with other hydrophobic amino acids. Substitutions that resulted in residue 341 having a smaller side-chain than residue 344 snitched the stoichiometry of the domain front 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 snitch 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.
引用
收藏
页码:6230 / 6236
页数:7
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