The structural basis for recognition of base J containing DNA by a novel DNA binding domain in JBP1
| العنوان: | The structural basis for recognition of base J containing DNA by a novel DNA binding domain in JBP1 |
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| المؤلفون: | Evangelos Christodoulou, Robbie P. Joosten, Sabrina Z. Jan, Dene R. Littler, Piet Borst, Patrick R. Griffin, Paul Wentworth, Anastassis Perrakis, Tatjana Heidebrecht, Henri G.A.M. van Luenen, Rajesh K. Grover, Bas ter Riet, Michael J. Chalmers |
| المساهمون: | Other departments, CCA -Cancer Center Amsterdam, Medical Biochemistry |
| المصدر: | Nucleic Acids Research Nucleic acids research, 39(13), 5715-5728. Oxford University Press |
| بيانات النشر: | Oxford University Press, 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | DNA, Bacterial, Models, Molecular, HMG-box, Base pair, Base J, Molecular Sequence Data, Protozoan Proteins, Biology, medicine.disease_cause, Arginine, Crystallography, X-Ray, Mass Spectrometry, chemistry.chemical_compound, Glucosides, X-Ray Diffraction, Structural Biology, Scattering, Small Angle, Genetics, medicine, Amino Acid Sequence, Uracil, Gene, Mutation, Aspartic Acid, Lysine, DNA-binding domain, DNA, Protein Structure, Tertiary, DNA-Binding Proteins, chemistry, Biochemistry, Sequence Alignment, In vitro recombination, Protein Binding |
| الوصف: | The J-binding protein 1 (JBP1) is essential for biosynthesis and maintenance of DNA base-J (β-d-glucosyl-hydroxymethyluracil). Base-J and JBP1 are confined to some pathogenic protozoa and are absent from higher eukaryotes, prokaryotes and viruses. We show that JBP1 recognizes J-containing DNA (J-DNA) through a 160-residue domain, DB-JBP1, with 10 000-fold preference over normal DNA. The crystal structure of DB-JBP1 revealed a helix-turn-helix variant fold, a 'helical bouquet' with a 'ribbon' helix encompassing the amino acids responsible for DNA binding. Mutation of a single residue (Asp525) in the ribbon helix abrogates specificity toward J-DNA. The same mutation renders JBP1 unable to rescue the targeted deletion of endogenous JBP1 genes in Leishmania and changes its distribution in the nucleus. Based on mutational analysis and hydrogen/deuterium-exchange mass-spectrometry data, a model of JBP1 bound to J-DNA was constructed and validated by small-angle X-ray scattering data. Our results open new possibilities for targeted prevention of J-DNA recognition as a therapeutic intervention for parasitic diseases. |
| اللغة: | English |
| تدمد: | 1362-4962 0305-1048 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9df426519900150a48129fbf2f2e3b60 http://europepmc.org/articles/PMC3141245 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....9df426519900150a48129fbf2f2e3b60 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13624962 03051048 |
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