1a1u
From Proteopedia
(New page: 200px<br /> <applet load="1a1u" size="450" color="white" frame="true" align="right" spinBox="true" caption="1a1u" /> '''SOLUTION STRUCTURE DETERMINATION OF A P53 M...) |
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'''SOLUTION STRUCTURE DETERMINATION OF A P53 MUTANT DIMERIZATION DOMAIN, NMR, MINIMIZED AVERAGE STRUCTURE'''<br /> | '''SOLUTION STRUCTURE DETERMINATION OF A P53 MUTANT DIMERIZATION DOMAIN, NMR, MINIMIZED AVERAGE STRUCTURE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The p53 tumor suppressor oligomerization domain, a dimer of two primary | + | 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. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1A1U is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1A1U is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1A1U OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Halezonetis, T | + | [[Category: Halezonetis, T D.]] |
| - | [[Category: Mccoy, M | + | [[Category: Mccoy, M A.]] |
| - | [[Category: Opella, S | + | [[Category: Opella, S J.]] |
| - | [[Category: Stavridi, E | + | [[Category: Stavridi, E S.]] |
| - | [[Category: Waterman, J | + | [[Category: Waterman, J L.F.]] |
[[Category: Wieczorek, A.]] | [[Category: Wieczorek, A.]] | ||
[[Category: anti-oncogene]] | [[Category: anti-oncogene]] | ||
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[[Category: p53]] | [[Category: p53]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:39:53 2008'' |
Revision as of 09:39, 21 February 2008
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SOLUTION STRUCTURE DETERMINATION OF A P53 MUTANT DIMERIZATION DOMAIN, NMR, MINIMIZED AVERAGE STRUCTURE
Contents |
Overview
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.
Disease
Known diseases associated with this structure: Adrenal cortical carcinoma OMIM:[191170], Breast cancer OMIM:[191170], Colorectal cancer OMIM:[191170], Hepatocellular carcinoma OMIM:[191170], Histiocytoma OMIM:[191170], Li-Fraumeni syndrome OMIM:[191170], Multiple malignancy syndrome OMIM:[191170], Nasopharyngeal carcinoma OMIM:[191170], Osteosarcoma OMIM:[191170], Pancreatic cancer OMIM:[191170], Thyroid carcinoma OMIM:[191170]
About this Structure
1A1U is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Hydrophobic side-chain size is a determinant of the three-dimensional structure of the p53 oligomerization domain., McCoy M, Stavridi ES, Waterman JL, Wieczorek AM, Opella SJ, Halazonetis TD, EMBO J. 1997 Oct 15;16(20):6230-6. PMID:9321402
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