Structural differences in the DNA binding domains of human p53 and its C. elegans ortholog Cep-1 Journal Article
| Authors: | Huyen, Y.; Jeffrey, P. D.; Derry, W. B.; Rothman, J. H.; Pavletich, N. P.; Stavridi, E. S.; Halazonetis, T. D. |
| Article Title: | Structural differences in the DNA binding domains of human p53 and its C. elegans ortholog Cep-1 |
| Abstract: | 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 α helices in Cep-1. The α 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 α 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. |
| Keywords: | controlled study; unclassified drug; nonhuman; protein domain; animals; structure-activity relationship; protein p53; data collection; dna; amino acid sequence; molecular sequence data; recombinant proteins; tumor suppressor protein p53; base sequence; dna structure; models, molecular; caenorhabditis elegans; protein folding; dna binding; crystallization; nematoda; protein structure, secondary; arginine; structural homology, protein; caenorhabditis elegans protein; orthology; caenorhabditis elegans proteins; alpha helix; caenorhabditis; humans; human; priority journal; article; caenorhabditis elegans p53 related 1 protein |
| Journal Title: | Structure |
| Volume: | 12 |
| Issue: | 7 |
| ISSN: | 0969-2126 |
| Publisher: | Cell Press |
| Date Published: | 2004-07-01 |
| Start Page: | 1237 |
| End Page: | 1243 |
| Language: | English |
| DOI: | 10.1016/j.str.2004.05.007 |
| PROVIDER: | scopus |
| PUBMED: | 15242600 |
| DOI/URL: | |
| Notes: | Structure -- Cited By (since 1996):34 -- Export Date: 16 June 2014 -- CODEN: STRUE -- Source: Scopus |
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