Binding Modes

The binding modes of a DNA or RNA binding protein refer to the different possible stable binding conformations between the protein and the nucleic acids. There are two main factors that can produce multiple modes of binding:

1. Many proteins can contain multiple DNA and RNA binding domains with different sequence-binding preferences. When different combinations of these domains bind to different binding sites, we refer to each DNA or RNA interacting combination as a binding mode of the protein.

2a. Many proteins can oligomerize into homo- and heterodimers and tetramers – whereby the protein-complex now has more DNA and/or RNA binding domains to bind to larger binding sites. In addition, many of these oligomerizing proteins can also bind as monomers to smaller sites. Often, differently sized protein-complexes have different binding properties and are referred to as having different binding modes. “Latent specificity” is when the binding specificity of a protein changes significantly when bound with different cofactors due to a change in the binding mode.

2b. Also, many binding sites of homo- and heterodimer transcription factors can have variable-length spacers between the two sequence-specific half-sites. Due to the helical twist and relative rigidity of double-stranded DNA, the length of the spacer in the binding site can significantly alter the binding specificity of the two surrounding half-sites – thereby conferring different binding modes.

* Caveat – Not everyone in the field agrees with the definitions stated above.