Structural Differences in the DNA Binding Domains of Human p53 and Its C. elegans Ortholog Cep-1
| Autor: | Thanos D. Halazonetis, W. Brent Derry, Joel H. Rothman, Elena S. Stavridi, Nikola P. Pavletich, Yentram Huyen, Philip D. Jeffrey |
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| Rok vydání: | 2004 |
| Předmět: |
Models
Molecular HMG-box Base pair Molecular Sequence Data Biology Protein Structure Secondary Structure-Activity Relationship Structural Biology Animals Humans Protein–DNA interaction Amino Acid Sequence B3 domain Caenorhabditis elegans Caenorhabditis elegans Proteins Molecular Biology Genetics Base Sequence Data Collection bZIP domain DNA-binding domain Recombinant Proteins Cell biology DNA binding site Structural Homology Protein Tumor Suppressor Protein p53 Crystallization Binding domain |
| Zdroj: | Structure. 12:1237-1243 |
| ISSN: | 0969-2126 |
| DOI: | 10.1016/j.str.2004.05.007 |
| Popis: | The DNA binding domains of human p53 and Cep-1, its C. elegans ortholog, recognize essentially identical DNA sequences despite poor sequence similarity. We solved the three-dimensional structure of the Cep-1 DNA binding domain in the absence of DNA and compared it to that of human p53. The two domains have similar overall folds. However, three loops, involved in DNA and Zn binding in human p53, contain small alpha helices in Cep-1. The alpha helix in loop L3 of Cep-1 orients the side chains of two conserved arginines toward DNA; in human p53, both arginines are mutation hotspots, but only one contacts DNA. The alpha helix in loop L1 of Cep-1 repositions the entire loop, making it unlikely for residues of this loop to contact bases in the major groove of DNA, as occurs in human p53. Thus, during evolution there have been considerable changes in the structure of the p53 DNA binding domain. |
| Databáze: | OpenAIRE |
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