A new look at the protein-DNA recognition codes

Konferenz: BIBE 2018 - International Conference on Biological Information and Biomedical Engineering
06.06.2018 - 08.06.2018 in Shanghai, China

Tagungsband: BIBE 2018

Seiten: 9Sprache: EnglischTyp: PDF

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Autoren:
Sun, Qing; Yan, Changhui (Department of Computer Science, North Dakota State University, Fargo, 58106, USA)

Inhalt:
For a long time, researchers have been searching for the protein-DNA “recognition codes”, which determine what DNA sequence a protein can bind to. This study investigates the recognition codes from a new angle, in which the preferred binding modes are captured using local structural motifs spanning the protein-DNA interfaces. Using product graph, we transformed the structural motif discovery problem into a search for maximal cliques. We studied two domains, Zinc-finger and Helix-Turn-Helix (HTH), that both used a recognition helix to interact with DNA. In each domain, we found a few frequent structural motifs spanning the protein-DNA interfaces. Each motif includes at least 2 amino acids and 1 nucleotide from both sides of the interfaces. The motifs specify not only the types of amino acids and nucleotides involved in the interaction, but also the distances between them and their relative orientation. These motifs reveal preferred binding modes at the interfaces that involve more entities than the traditional contacting pairs, and thus have the benefit of being more specific. At the same time, these are local motifs that don’t require any assumption about the global structures of the protein and DNA. Thus, they have the potential to allow researchers to “read out” the DNA sequence based on local structures of the protein. The biological and statistical significance of the motifs were confirmed using evolutionary conservation analysis and bootstrapping. Comparison between the two domains also revealed motif that was used widely in various types of protein-DNA interactions.