Effect of Zn2+ on DNA Recognition and Stability of the p53 DNA-Binding Domain
Zinc ions are frequently found in DNA-binding proteins. p53 is a cancer-related transcriptional factor, and its DNA-binding domain (DBD) contains a Zn2+, which has been shown to be important for aggregation and sequence-specific DNA binding. We have carried out molecular dynamics simulations to inve...
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Published in | Biochemistry (Easton) Vol. 45; no. 24; pp. 7483 - 7492 |
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Main Authors | , |
Format | Journal Article |
Language | English |
Published |
United States
American Chemical Society
20.06.2006
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Abstract | Zinc ions are frequently found in DNA-binding proteins. p53 is a cancer-related transcriptional factor, and its DNA-binding domain (DBD) contains a Zn2+, which has been shown to be important for aggregation and sequence-specific DNA binding. We have carried out molecular dynamics simulations to investigate the influence of Zn2+ on the p53 DNA recognition and the stability of the DBD. In the simulation with Zn2+ present, the protein attracted to the DNA phosphate backbone, allowing for Arg248 on loop L3 to be inserted into the minor groove for specific contact with the DNA base. The insertion of Arg248 between the backbone phosphate groups in the minor groove caused a narrowing of the minor groove, which is not seen in the simulation without Zn2+. Structurally, the zinc ion coordinated the motions among the different protein structural elements, which could also be important for optimal binding and core packing. The influence of Zn2+ on protein stability was mainly localized to the L2 loop. Our results suggest that L2 may be a frustrated and highly flexible element and play an important role in aggregation of Zn-free p53. Zn2+ keeps the L2 structured and probably prevents aggregation. |
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AbstractList | Zinc ions are frequently found in DNA-binding proteins. p53 is a cancer-related transcriptional factor, and its DNA-binding domain (DBD) contains a Zn2+, which has been shown to be important for aggregation and sequence-specific DNA binding. We have carried out molecular dynamics simulations to investigate the influence of Zn2+ on the p53 DNA recognition and the stability of the DBD. In the simulation with Zn2+ present, the protein attracted to the DNA phosphate backbone, allowing for Arg248 on loop L3 to be inserted into the minor groove for specific contact with the DNA base. The insertion of Arg248 between the backbone phosphate groups in the minor groove caused a narrowing of the minor groove, which is not seen in the simulation without Zn2+. Structurally, the zinc ion coordinated the motions among the different protein structural elements, which could also be important for optimal binding and core packing. The influence of Zn2+ on protein stability was mainly localized to the L2 loop. Our results suggest that L2 may be a frustrated and highly flexible element and play an important role in aggregation of Zn-free p53. Zn2+ keeps the L2 structured and probably prevents aggregation. |
Author | Nilsson, Lennart Duan, Jianxin |
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Snippet | Zinc ions are frequently found in DNA-binding proteins. p53 is a cancer-related transcriptional factor, and its DNA-binding domain (DBD) contains a Zn2+, which... |
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SubjectTerms | Arginine - chemistry Arginine - genetics Cations, Divalent - chemistry Computer Simulation DNA - chemistry DNA - genetics DNA-Binding Proteins - chemistry DNA-Binding Proteins - genetics Hydrogen Bonding Medicin och hälsovetenskap Models, Molecular Molecular Conformation Nucleic Acid Conformation Protein Binding - genetics Protein Structure, Secondary - genetics Protein Structure, Tertiary - genetics Static Electricity Thermodynamics Tumor Suppressor Protein p53 - chemistry Tumor Suppressor Protein p53 - genetics Tumor Suppressor Protein p53 - metabolism Zinc - chemistry |
Title | Effect of Zn2+ on DNA Recognition and Stability of the p53 DNA-Binding Domain |
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