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

Tatjana Heidebrecht, Evangelos Christodoulou, Michael J. Chalmers, Sabrina Jan, Bas Ter Riet, Rajesh K. Grover, Robbie P Joosten, Dene Littler, Henri Van Luenen, Patrick R. Griffin, Paul Wentworth, Piet Borst, Anastassis Perrakis

Research output: Contribution to journalReview ArticleResearchpeer-review

19 Citations (Scopus)


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 10000-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.

Original languageEnglish
Pages (from-to)5715-5728
Number of pages14
JournalNucleic Acids Research
Issue number13
Publication statusPublished - Jul 2011
Externally publishedYes

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