The role of DNA shape in protein-DNA recognition

By R. Rohs, S. West, Alona Sosinsky, Peng Liu, R. Mann, Barry Honig. Nature, 2009

1,081 citations recorded by the source corpus.

The recognition of specific DNA sequences by proteins is thought to depend on two types of mechanism: one that involves the formation of hydrogen bonds with specific bases, primarily in the major groove, and one involving sequence-dependent deformations of the DNA helix. By comprehensively analysing the three-dimensional structures of protein–DNA complexes, here we show that the binding of arginine residues to narrow minor grooves is a widely used mode for protein–DNA recognition. This readout mechanism exploits the phenomenon that narrow minor grooves strongly enhance the negative electrostatic potential of the DNA. The nucleosome core particle offers a prominent example of this effect. Minor-groove narrowing is often associated with the presence of A-tracts, AT-rich sequences that exclude the flexible TpA step. These findings indicate that the ability to detect local variations in DNA shape and electrostatic potential is a general mechanism that enables proteins to use information in the minor groove, which otherwise offers few opportunities for the formation of base-specific hydrogen bonds, to achieve DNA-binding specificity.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/fef6149954b402c7a99d8c12c0494f53aeacf196

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Citations in the corpus

Homeodomain proteins: an update (2015, background): “Arginine residues are preferentially found in narrowminor grooves, which tend to be A-tracts (Rohs et al. 2009).”
Basset: learning the regulatory code of the accessible genome with deep convolutional neural networks (2015, background): “So-called A-tracts are known to narrow the minor groove of the DNA double helix (Rohs et al. 2009).”
The Human Transcription Factors. (2018, neutral): “PWM: there may be dependencies among base positions (Bulyk et al., 2002; Jolma et al., 2013), for example, due toDNA shape or deformability (Rohs et al., 2009); the TF may have multiple binding modes (e.g., different physical configurations of the protein leading to separate, distinct motifs)…”
Distinct Structures and Dynamics of Chromatosomes with Different Human Linker Histone Isoforms (2020, background): “4 chromatosome, a possible interpretation of the binding preference is that the linker histone uses an Arg residue to interact with the minor groove of the linker DNA with more AT base pair (Figures 2C, 2E, and 2F), similar to the interactions between core histones and the DNA in the nucleosome core”
Crystal structure of Cpf1 in complex with guide RNA and target DNA (2016, background): “Recognition of the 50-TTTN-30 PAM The PAM duplex adopts a distorted conformation with a narrow minor groove, as often observed in AT-rich DNA (Rohs et al., 2009), and is bound to the groove formed by the WED, REC1, and PI domains (Figures 5A and S5A).”
Extensive protein and DNA backbone sampling improves structure-based specificity prediction for C2H2 zinc fingers (2011, background): “It is likely that there are higher-order sequence-dependencies, for example A-tract conformational preferences (10), that can only be captured by considering longer-range interactions.”
Making the Bend: DNA Tertiary Structure and Protein-DNA Interactions (2014, background): “For instance, transcription factors (TFs) achieve in vivo unique sequence specificity with seemingly identical DNA motifs but distinct targets.”
DNAshape: a method for the high-throughput prediction of DNA structural features on a genomic scale (2013, methodology): “Based on the many more highresolution structures that have been solved and analysed in recent years, it is now apparent that longer DNA segments must be characterized to capture the sequence– structure degeneracy of DNA (1).”
Origins of specificity in protein-DNA recognition (2010, positive): “Because narrow minor grooves are often associated with AT-rich sequences (Table 2), enhancement of negative electrostatic potential in the minor groove, which, in turn, is recognized by arginines, offers a general mechanism for sequence-specific recognition of DNA shape (66).”
DNA-binding specificities of human transcription factors. (2013, positive): “A third type of binding that depends on DNA minor groove shape and confers partial sequence specificity has been suggested based on analysis of crystal structures of proteinDNA complexes (Aggarwal et al., 1988; Rohs et al., 2009; Zheng et al., 1999).”