Origins of specificity in protein-DNA recognition

By R. Rohs, Xiangshu Jin, S. West, Rohit Joshi, Barry Honig, R. Mann. 2010

907 citations recorded by the source corpus.

Specific interactions between proteins and DNA are fundamental to many biological processes. In this review, we provide a revised view of protein-DNA interactions that emphasizes the importance of the three-dimensional structures of both macromolecules. We divide protein-DNA interactions into two categories: those where the protein recognizes the unique chemical signatures of the DNA bases (base readout) and those where the protein recognizes a sequence-dependent DNA shape (shape readout). We further divide base readout into those interactions that occur in the major groove from those that occur in the minor groove. Analogously, the readout of DNA shape is subdivided into global shape recognition, for example when the DNA helix exhibits an overall bend, and local shape recognition, for example when a base pair step is kinked or when a region of the minor groove is narrow. Based on the >1500 structures of protein-DNA complexes now available in the Protein Data Base, we argue that individual DNA binding proteins combine multiple readout mechanisms to achieve DNA binding specificity. Specificity that distinguishes between families frequently involves base readout in the major groove while shape readout is often exploited for higher resolution specificity, to distinguish between members within the same DNA-binding protein family.

Subfields: Molecular Biology

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Citations in the corpus

A comparative analysis of transcription factor binding models learned from PBM, HT-SELEX and ChIP data (2014, background): “the HMG proteins, for which structure plays a larger role in binding (21)].”
Chemistry, structure and function of approved oligonucleotide therapeutics (2023, background): “The negative charges of phosphates are dotting the outside and the grooves created by the two strands winding around each other represent regions of varying negative electrostatic potential (95).”
Predicting the sequence specificities of DNA- and RNA-binding proteins by deep learning (2015, background): “However, growing evidence indicates that sequence specificities can be more accurately captured by more complex techniques 2–5 .”
Making the Bend: DNA Tertiary Structure and Protein-DNA Interactions (2014, background): “There are two mechanisms by which proteins specifically recognise a particular DNA: the base readout and the shape readout (reviewed in [85]).”
DNA-binding specificities of human transcription factors. (2013, positive): “However, strong base interdependencies were observed in a stretch of three to five A or T residues flanking the core binding site in multiple TF classes, consistent with proposed shape-based recognition of DNA (Rohs et al., 2010).”
DNAshape: a method for the high-throughput prediction of DNA structural features on a genomic scale (2013, background): “Our previous work and that by others established MGW as an important feature of DNA shape (1,2).”
Conservation of transcription factor binding specificities across 600 million years of bilateria evolution (2015, background): “However, in addition to the primary specificity, many TFs have secondary modes of DNA binding, can recognize multiple different homodimeric sites and/or recognize multiple different sequences based on DNA shape (Badis et al., 2009; Rohs et al., 2010; Jolma et al., 2013).”