Cited by 1,096DNA and Nucleic Acid ChemistryDiffusion and Search DynamicsGenomics and Chromatin Dynamics

The role of DNA shape in protein–DNA recognition

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Rohs, Remo, West, Sean M., Sosinsky, Alona, Liu, Peng, Mann, Richard S., Honig, Barry·2009·Nature

Abstract

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.

    “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

    The Abstract (page unavailable) says DNA bending can optimize a protein–DNA interface, and the Concluding remarks (page unavailable) link propeller twisting to minor-groove shape and specific protein interactions. The paper also describes transcription-factor-specific recognition of local DNA shape, but the passages do not support shearing as a binding mechanism; a search for “shearing” found no matching discussion. (LLM, conf=0.85)

    Experimental — accuracy not yet measured
  • The L1 loop formed contacts with DNA in the minor groove (shape readout).

    “The L1 loop formed contacts with DNA in the minor groove (shape readout) 24 .”

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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
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
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

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