2XSE

The structural basis for recognition of J-base containing DNA by a novel DNA-binding domain in JBP1

Summary for 2XSE

• Entry DOI: 10.2210/pdb2xse/pdb
• Descriptor: THYMINE DIOXYGENASE JBP1, NITRATE ION, GLYCEROL, ... (4 entities in total)
• Functional Keywords: oxidoreductase, dna-binding
• Biological source: LEISHMANIA TARENTOLAE
• Cellular location: Nucleus: Q9U6M1
• Total number of polymer chains: 1
• Total formula weight: 20691.44

Authors

Heidebrecht, T.,Christodoulou, E.,Chalmers, M.J.,Jan, S.,ter Riete, B.,Grover, R.K.,Joosten, R.P.,Littler, D.,vanLuenen, H.,Griffin, P.R.,Wentworth, P.,Borst, P.,Perrakis, A. (deposition date: 2010-09-28, release date: 2011-03-30, Last modification date: 2024-11-06)

Primary citation

Heidebrecht, T.,Christodoulou, E.,Chalmers, M.J.,Jan, S.,Ter Riet, B.,Grover, R.K.,Joosten, R.P.,Littler, D.,Van Luenen, H.,Griffin, P.R.,Wentworth, P.,Borst, P.,Perrakis, A.
The Structural Basis for Recognition of Base J Containing DNA by a Novel DNA Binding Domain in Jbp1.
Nucleic Acids Res., 39:5715-, 2011

PubMed Abstract: 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.

PubMed: 21415010
DOI: 10.1093/NAR/GKR125

Experimental method

X-RAY DIFFRACTION (1.9 Å)