Abstract
The interaction of nucleic acids with proteins plays an important role in many fundamental biological processes in living cells, including replication, transcription, and translation. Therefore, understanding nucleic acid–protein interaction is of high relevance in many areas of biology, medicine and technology. During almost four decades of its existence atomic force microscopy (AFM) accumulated a significant experience in investigation of biological molecules at a single-molecule level. AFM has become a powerful tool of molecular biology and biophysics providing unique information about properties, structure, and functioning of biomolecules. Despite a great variety of nucleic acid–protein systems under AFM investigations, there are a number of typical approaches for such studies. This review is devoted to the analysis of the typical AFM-based approaches of investigation of DNA (RNA)–protein complexes with a major focus on transcription studies. The basic strategies of AFM analysis of nucleic acid–protein complexes including investigation of the products of DNA–protein reactions and real-time dynamics of DNA–protein interaction are categorized and described by the example of the most relevant research studies. The described approaches and protocols have many universal features and, therefore, are applicable for future AFM studies of various nucleic acid–protein systems.
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Adapted from Bonini et al. (2022) under the CC 4.0 license (http://creativecommons.org/licenses/by/4.0/). b AFM image of the complex of streptavidin labeled 1653 bp DNA fragment, comprising the dual-promoter template (153 bp), with TFAM. Streptavidin label is marked by arrow no. 1, DNA bound TFAM is marked by arrow no. 2. 3-Aminopropyl-trietoxy silatrane modified mica was used as a substrate. AFM image was obtained in a buffer (25 mM NaCl, 25 mM Hepes at pH 7.5). Reproduced from Uchida et al. (2017) under the CC 4.0 license (http://creativecommons.org/licenses/by/4.0/)
Reproduced from Chammas et al. (2017) under the CC 4.0 license (http://creativecommons.org/licenses/by/4.0/)
Reproduced from Shin et al. (2005) under the CC 4.0 license (http://creativecommons.org/licenses/by/4.0/)
Reproduced from Yamanaka et al. (2018) under the CC 4.0 license (http://creativecommons.org/licenses/by/4.0/)
Reproduced from Yang et al. (2005) under the Creative Commons CC BY license (http://creativecommons.org/licenses/by/4.0/)
Reproduced from Crampton et al. (2006) under the CC BY-NC 2.0 UK license (https://creativecommons.org/licenses/by-nc/2.0/uk/)
Reproduced from Bustamante et al. (1999) under the CC 4.0 license (http://creativecommons.org/licenses/by/4.0/). b Time-lapse AFM images of stalled elongation complexes (E.coli RNAP–pSF-OXB19 DNA) adsorbed on a stearylamine-modified HOPG surface (images 1–2) before and (images 3–4) after the addition of nucleoside triphosphates (NTP). The E.coli RNAP molecule is denoted by the arrow. The time (in min) of each AFM image relative to the first AFM image in the sequence is shown at the bottom left. The scan size is 500 × 500 nm2. AFM images were obtained in the buffer. Reprinted with permission from Dubrovin et al. (2017). Copyright (2017) American Chemical Society
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Data availability
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Abbreviations
- 5mC:
-
5-Methylcytosine
- DinJ-YafQ:
-
Bacterial toxin-antitoxin system
- Dps:
-
DNA-binding protein from starved cells
- EMSA:
-
Electrophoretic mobility shift assay
- FIS:
-
Factor for inversion stimulation of the homologous Hin and Gin site-specific DNA recombinases of Salmonella and phage Mu
- GaIR:
-
GaI repressor
- GM:
-
N,N’-(decane-1,10-diyl)bis(tetraglycineamide)
- H-NS:
-
Histone-like nucleoid-structuring protein
- HS-AFM:
-
High-speed AFM
- HSE:
-
Heat shock elements
- HSF2:
-
Human heat shock transcription factor 2
- NtrC:
-
Nitrogen-regulatory protein
- OPC:
-
Open promoter complex
- RNAP:
-
RNA polymerase
- TFAM:
-
Mitochondrial transcription factor A
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Funding
This work was supported by the Ministry of Science and Higher Education of the Russian Federation (Goszadaniye) 075–03-2023–106, project no. FSMG-2023–0015 (Sects. 1–5) and the Sirius University of Science and Technology, project no. BMA-RND-2007 (Sects. 6–10).
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Dubrovin, E.V. Atomic force microscopy-based approaches for single-molecule investigation of nucleic acid–protein complexes. Biophys Rev 15, 1015–1033 (2023). https://doi.org/10.1007/s12551-023-01111-3
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DOI: https://doi.org/10.1007/s12551-023-01111-3