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Despite the negative charge of the DNA backbone, acidic residues (Asp/Glu) commonly participate in the base readout, with a strong preference for cytosine. In fact, in the solved DNA/protein structures, cytosine is recognized almost exclusively by Asp/Glu through a direct hydrogen bond, while at the same time, adenine, regardless of its amino group, shows no propensity for Asp/Glu. Here, we analyzed the contribution of Asp/Glu to sequence-specific DNA binding using classical and ab initio simulations of selected transcription factors and found that it is governed by a fine balance between the repulsion from backbone phosphates and attractive interactions with cytosine. Specifically, Asp/Glu lower the affinity for noncytosine sites and thus act as negative selectors preventing off-target binding. At cytosine-containing sites, the favorable contribution does not merely rely on the formation of a single H-bond but usually requires the presence of positive potential generated by multiple cytosines, consistently with the observed excess of cytosine in the target sites. Finally, we show that the preference of Asp/Glu for cytosine over adenine is a result of the repulsion from the adenine imidazole ring and a tendency of purine–purine dinucleotides to adopt the BII conformation.
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- Wersja publikacji
- Accepted albo Published Version
- DOI:
- Cyfrowy identyfikator dokumentu elektronicznego (otwiera się w nowej karcie) 10.1073/pnas.2212501120
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- Kategoria:
- Publikacja w czasopiśmie
- Typ:
- artykuły w czasopismach
- Opublikowano w:
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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
nr 120,
ISSN: 0027-8424 - Język:
- angielski
- Rok wydania:
- 2023
- Opis bibliograficzny:
- Hossain K., Kogut M., Słabońska J., Sappati S., Wieczór M., Czub J.: How acidic amino acid residues facilitate DNA target site selection// PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA -Vol. 120,iss. 3 (2023),
- DOI:
- Cyfrowy identyfikator dokumentu elektronicznego (otwiera się w nowej karcie) 10.1073/pnas.2212501120
- Źródła finansowania:
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- COST_FREE
- Weryfikacja:
- Politechnika Gdańska
wyświetlono 110 razy