2j10
From Proteopedia
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|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1a1u|1A1U]], [[1aie|1AIE]], [[1c26|1C26]], [[1dt7|1DT7]], [[1gzh|1GZH]], [[1h26|1H26]], [[1hs5|1HS5]], [[1jsp|1JSP]], [[1kzy|1KZY]], [[1ma3|1MA3]], [[1olg|1OLG]], [[1olh|1OLH]], [[1pes|1PES]], [[1pet|1PET]], [[1sae|1SAE]], [[1saf|1SAF]], [[1sag|1SAG]], [[1sah|1SAH]], [[1sai|1SAI]], [[1saj|1SAJ]], [[1sak|1SAK]], [[1sal|1SAL]], [[1tsr|1TSR]], [[1tup|1TUP]], [[1uol|1UOL]], [[1xqh|1XQH]], [[1ycq|1YCQ]], [[1ycr|1YCR]], [[1ycs|1YCS]], [[2ac0|2AC0]], [[2ady|2ADY]], [[2ahi|2AHI]], [[2ata|2ATA]], [[2b3g|2B3G]], [[2bim|2BIM]], [[2bin|2BIN]], [[2bio|2BIO]], [[2bip|2BIP]], [[2biq|2BIQ]], [[2f1x|2F1X]], [[2fej|2FEJ]], [[2j0z|2J0Z]], [[2j11|2J11]], [[3sak|3SAK]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2j10 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j10 OCA], [http://www.ebi.ac.uk/pdbsum/2j10 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2j10 RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
The role of hydrophobic amino acids in the formation of hydrophobic cores as one of the major driving forces in protein folding has been extensively studied. However, the implication of neutral solvent-exposed amino acids is less clear and available information is scarce. We have used a combinatorial approach to study the structural relevance of three solvent-exposed residues (Tyr(327), Thr(329), and Gln(331)) located in thebeta-sheet of the tetramerization domain of the tumor suppressor p53 (p53TD). A conformationally defined peptide library was designed where these three positions were randomized. The library was screened for tetramer stability. A set of p53TD mutants containing putative stabilizing or destabilizing residue combinations was synthesized for a thermodynamic characterization. Unfolding experiments showed a wide range of stabilities, with T(m) values between 27 and 83 degrees C. Wild type p53TD and some highly destabilized and stabilized mutants were further characterized. Thermodynamic and biophysical data indicated that these proteins were folded tetramers, with the same overall structure, in equilibrium with unfolded monomers. An NMR study confirmed that the main structural features of p53TD are conserved in all the mutants analyzed. The thermodynamic stability of the different p53TD mutants showed a strong correlation with parameters that favor formation and stabilization of the beta-sheet. We propose that stabilization through hydrophobic interactions of key secondary structure elements might be the underlying mechanism for the strong influence of solvent-exposed residues in the stability of p53TD. Proteins 2007. (c) 2007 Wiley-Liss, Inc. | The role of hydrophobic amino acids in the formation of hydrophobic cores as one of the major driving forces in protein folding has been extensively studied. However, the implication of neutral solvent-exposed amino acids is less clear and available information is scarce. We have used a combinatorial approach to study the structural relevance of three solvent-exposed residues (Tyr(327), Thr(329), and Gln(331)) located in thebeta-sheet of the tetramerization domain of the tumor suppressor p53 (p53TD). A conformationally defined peptide library was designed where these three positions were randomized. The library was screened for tetramer stability. A set of p53TD mutants containing putative stabilizing or destabilizing residue combinations was synthesized for a thermodynamic characterization. Unfolding experiments showed a wide range of stabilities, with T(m) values between 27 and 83 degrees C. Wild type p53TD and some highly destabilized and stabilized mutants were further characterized. Thermodynamic and biophysical data indicated that these proteins were folded tetramers, with the same overall structure, in equilibrium with unfolded monomers. An NMR study confirmed that the main structural features of p53TD are conserved in all the mutants analyzed. The thermodynamic stability of the different p53TD mutants showed a strong correlation with parameters that favor formation and stabilization of the beta-sheet. We propose that stabilization through hydrophobic interactions of key secondary structure elements might be the underlying mechanism for the strong influence of solvent-exposed residues in the stability of p53TD. Proteins 2007. (c) 2007 Wiley-Liss, Inc. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Adrenal cortical carcinoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Breast cancer OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Colorectal cancer OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Hepatocellular carcinoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Histiocytoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Li-Fraumeni syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Multiple malignancy syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Nasopharyngeal carcinoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Osteosarcoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Pancreatic cancer OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]], Thyroid carcinoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191170 191170]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: zinc]] | [[Category: zinc]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:51:34 2008'' |
Revision as of 00:51, 31 March 2008
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| Related: | 1A1U, 1AIE, 1C26, 1DT7, 1GZH, 1H26, 1HS5, 1JSP, 1KZY, 1MA3, 1OLG, 1OLH, 1PES, 1PET, 1SAE, 1SAF, 1SAG, 1SAH, 1SAI, 1SAJ, 1SAK, 1SAL, 1TSR, 1TUP, 1UOL, 1XQH, 1YCQ, 1YCR, 1YCS, 2AC0, 2ADY, 2AHI, 2ATA, 2B3G, 2BIM, 2BIN, 2BIO, 2BIP, 2BIQ, 2F1X, 2FEJ, 2J0Z, 2J11, 3SAK
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
P53 TETRAMERIZATION DOMAIN MUTANT T329F Q331K
Overview
The role of hydrophobic amino acids in the formation of hydrophobic cores as one of the major driving forces in protein folding has been extensively studied. However, the implication of neutral solvent-exposed amino acids is less clear and available information is scarce. We have used a combinatorial approach to study the structural relevance of three solvent-exposed residues (Tyr(327), Thr(329), and Gln(331)) located in thebeta-sheet of the tetramerization domain of the tumor suppressor p53 (p53TD). A conformationally defined peptide library was designed where these three positions were randomized. The library was screened for tetramer stability. A set of p53TD mutants containing putative stabilizing or destabilizing residue combinations was synthesized for a thermodynamic characterization. Unfolding experiments showed a wide range of stabilities, with T(m) values between 27 and 83 degrees C. Wild type p53TD and some highly destabilized and stabilized mutants were further characterized. Thermodynamic and biophysical data indicated that these proteins were folded tetramers, with the same overall structure, in equilibrium with unfolded monomers. An NMR study confirmed that the main structural features of p53TD are conserved in all the mutants analyzed. The thermodynamic stability of the different p53TD mutants showed a strong correlation with parameters that favor formation and stabilization of the beta-sheet. We propose that stabilization through hydrophobic interactions of key secondary structure elements might be the underlying mechanism for the strong influence of solvent-exposed residues in the stability of p53TD. Proteins 2007. (c) 2007 Wiley-Liss, Inc.
About this Structure
2J10 is a Single protein structure of sequence from [1]. Full crystallographic information is available from OCA.
Reference
Solvent-exposed residues located in the beta-sheet modulate the stability of the tetramerization domain of p53-A structural and combinatorial approach., Mora P, Carbajo RJ, Pineda-Lucena A, Sanchez Del Pino MM, Perez-Paya E, Proteins. 2007 Dec 12;. PMID:18076077
Page seeded by OCA on Mon Mar 31 03:51:34 2008
Categories: Single protein | Carbajo, R J. | Mora, P. | Perez-Paya, E. | Pineda-Lucena, A. | Pino, M M.Sanchez Del. | Acetylation | Activator | Alternative splicing | Anti-oncogene | Apoptosis | Cell cycle | Disease mutation | Dna-binding | Glycoprotein | Host-virus interaction | Li-fraumeni syndrome | Metal-binding | Nuclear protein | P53 | Phosphorylation | Polymorphism | Tetramerization domain | Transcription | Transcription regulation | Wild type | Zinc
