Nucleic acids and chromatin
Nucleic acids and chromatin

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6.4 Non-specific DNA-protein interactions

As we saw above, most sequence-specific DNA binding proteins recognise and bind to their target DNA sequence with a high affinity by utilising structural domains that make sequence-specific contacts with the DNA bases in the major groove. These contacts utilise extensive non-covalent bonding and hydrophobic interactions. In contrast, non-specific protein–DNA interactions occur with much lower affinity. The reason for this low binding affinity is that most non-sequence-specific interactions between protein and DNA involve only weak interactions, primarily electrostatic in nature, between the protein and the negatively charged DNA backbone.

SAQ 28

What proteins, that you have already encountered, must interact with DNA in this manner?


Your examples could include DNA topoisomerases, DNA polymerase and RNA polymerase, all of which must interact very closely with DNA.

The major feature of proteins that interact with DNA in a non-sequence-specific manner is that they contain surfaces or structures that carry positively charged amino acid side-chains. Various common protein structures provide a framework for placement of these basic amino acids in positions that are complementary to the arrangement of phosphates, either along the DNA backbone or across the minor and major grooves. These protein structures include helices and antiparallel  β strands that can interact electrostatically with the major or minor groove phosphates, which are approximately 7 Å apart along the phosphate–deoxyribose backbone. In the case of helices, the positioning of basic residues on the external faces of the helix could influence DNA-binding preferences and the recognition of either a particular local structure or the global configuration of the DNA. An example of a common motif is the SPKK motif ([Ser/Thr]–Pro–[Lys/Arg]–[Lys/Arg]), which is found in a variety of proteins that bind to the minor groove of DNA.

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