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The role of DNA shape in protein–DNA recognition
Open accessAbstract
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.
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“Twisting, bending, and shearing of DNA influence local binding in a TF-specific fashion (Rohs et al., 2009).”
From WILDS: A Benchmark of in-the-Wild Distribution Shifts (2020) · cites this paper as Rohs et al., 2009
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“The L1 loop formed contacts with DNA in the minor groove (shape readout) 24 .”
From Mechanistic insights into metal ion activation and operator recognition by the ferric uptake regulator (2015) · cites this paper as [24]
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Metadata
- Authors
- Rohs, R., West, S. M., Sosinsky, A., Liu, P., Mann, R. S., & Honig, B.
- Affiliations
- Howard Hughes Medical Institute (US)
- Columbia University (US)
- Corresponding author
- Mann, Richard S.
- Honig, Barry
- Venue
- Nature
- Published
- 2009-10
- Volume
- 461
- Issue
- 7268
- Pages
- 1248-1253
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2793086
- OpenAlex
- W2012627860
- Cited by
- 1,096
- References
- 51
- Citations by year
- 2026: 51 · 2025: 68 · 2024: 73 · 2023: 66 · 2022: 77 · 2021: 76 · 2020: 58 · 2019: 57 · 2018: 55 · 2017: 65 · 2016: 52 · 2015: 76 · 2014: 72 · 2013: 74 · 2012: 64
- FWCI
- 23.46
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- BIROn (Birkbeck, University of London) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Cancer Institute (U54CA121852)
- National Institute of General Medical Sciences (GM54510, R01GM030518, R01GM054510)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Diffusion and Search Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- protein-DNA recognition, DNA shape, minor groove, major groove, arginine binding, nucleosome core particle, A-tracts, sequence-specific DNA-binding proteins, DNA binding specificity, protein-DNA complex, hydrogen bonding
- MeSH terms
- Animals, Arginine, Base Sequence, DNA, DNA-Binding Proteins, Hydrogen Bonding, Lysine, Nucleic Acid Conformation, Nucleosomes, Protein Binding, Saccharomyces cerevisiae, Databases, Factual, AT Rich Sequence, Static Electricity
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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