Understanding the structural details of APOBEC3-DNA interactions using graph-based representations
| Autor: | Joseph Chi Fung Ng, Franca Fraternali |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Computer science
In silico APOBEC3 Computational biology Protein structural networks DNA sequencing Homology (biology) Article chemistry.chemical_compound Structural bioinformatics chemistry lcsh:Biology (General) Structural Biology RNA editing Protein–DNA interaction Human genome Molecular Biology lcsh:QH301-705.5 DNA Protein-DNA interaction |
| Zdroj: | Current Research in Structural Biology, Vol 2, Iss, Pp 130-143 (2020) Current Research in Structural Biology |
| Popis: | Human APOBEC3 (A3; apolipoprotein B mRNA editing catalytic polypeptide-like 3) is a family of seven enzymes involved in generating mutations in nascent reverse transcripts of many retroviruses, as well as the human genome in a range of cancer types. The structural details of the interaction between A3 proteins and DNA molecules are only available for a few family members. Here we use homology modelling techniques to address the difference in structural coverage of human A3 enzymes interacting with different DNA substrates. A3-DNA interfaces are represented as residue networks ("graphs"), based on which features at these interfaces are compared and quantified. We demonstrate that graph-based representations are effective in highlighting structural features of A3-DNA interfaces. By large-scale in silico mutagenesis of the bound DNA chain, we predicted the preference of substrate DNA sequence for multiple A3 domains. These data suggested that computational modelling approaches could contribute in the exploration of the structural basis for sequence specificity in A3 substrate selection, and demonstrated the utility of graph-based approaches in evaluating a large number of structural models generated in silico. Graphical abstract Image 1 Highlights • APOBEC3(A3)-DNA structures have been resolved with modified deaminase domains. • Structural modelling of interaction between wild-type A3 domains and DNA substrates. • Graph-based representations reveal structural differences across A3-DNA interfaces. • Using in silico mutagenesis we compared substrate preference of multiple A3 domains. • Graph-based approaches can efficiently compare a large number of structural models. |
| Databáze: | OpenAIRE |
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