Structural Characterization of Protein–Nucleic Acid Complexes: An Overview of the Recent Innovation in the Analytic Methods

Bellone, Maria Laura; Mensitieri, Francesca; Marmo, Elvira; Calabrese, Alessia Nunzia; Gaudino, Giulia; Izzo, Viviana; Dal Piaz, Fabrizio

doi:10.3390/ijms262311465

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Structural Characterization of Protein–Nucleic Acid Complexes: An Overview of the Recent Innovation in the Analytic Methods

by

Maria Laura Bellone

^1,2,*,†,

Francesca Mensitieri

^2,3,*,†,

Elvira Marmo

²,

Alessia Nunzia Calabrese

^2,3,

Giulia Gaudino

²,

Viviana Izzo

^2,4

and

Fabrizio Dal Piaz

^2,4

¹

Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 84084 Fisciano, Italy

²

Department of Medicine and Surgery, University of Salerno, Via Giovanni Paolo II, 84081 Baronissi, Italy

³

School of Specialization in Clinical Pathology and Clinical Biochemistry, University of Salerno, Via Giovanni Paolo II, 84081 Baronissi, Italy

⁴

AOU San Giovanni di Dio e Ruggi d’Aragona Hospital, 84131 Salerno, Italy

^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Int. J. Mol. Sci. 2025, 26(23), 11465; https://doi.org/10.3390/ijms262311465 (registering DOI)

Submission received: 31 October 2025 / Revised: 21 November 2025 / Accepted: 23 November 2025 / Published: 26 November 2025

(This article belongs to the Special Issue Innovative Approaches for Investigations on Protein Interactions)

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Abstract

The study of gene expression regulation systems, transcriptional, post-transcriptional, and translational processes require in-depth knowledge of the structure and dynamics of protein–DNA and protein–RNA complexes. Furthermore, the discovery of the multiple roles played by different types of RNA, including within extracellular vesicles, has raised new questions about the systems responsible for stabilizing and transporting these RNAs. Over the years, numerous experimental approaches have been developed for the study of complexes between proteins and nucleic acids, both in terms of the type and degree of accuracy of the information they are able to provide. Furthermore, some techniques have proven suitable for monitoring dynamic processes, while others provide very high-resolution data. Finally, the different methods also differ in their applicability directly to the study of complexes within their biological environment, while others can only be used on purified samples. The purpose of this review is to provide an overview of many of these approaches, accompanied by some examples of recent applications, to highlight their strengths and limitations.

Keywords: microscopy; cryo-EM; coimmunoprecipitation; proximity label; surface plasmon resonance

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MDPI and ACS Style

Bellone, M.L.; Mensitieri, F.; Marmo, E.; Calabrese, A.N.; Gaudino, G.; Izzo, V.; Dal Piaz, F. Structural Characterization of Protein–Nucleic Acid Complexes: An Overview of the Recent Innovation in the Analytic Methods. Int. J. Mol. Sci. 2025, 26, 11465. https://doi.org/10.3390/ijms262311465

AMA Style

Bellone ML, Mensitieri F, Marmo E, Calabrese AN, Gaudino G, Izzo V, Dal Piaz F. Structural Characterization of Protein–Nucleic Acid Complexes: An Overview of the Recent Innovation in the Analytic Methods. International Journal of Molecular Sciences. 2025; 26(23):11465. https://doi.org/10.3390/ijms262311465

Chicago/Turabian Style

Bellone, Maria Laura, Francesca Mensitieri, Elvira Marmo, Alessia Nunzia Calabrese, Giulia Gaudino, Viviana Izzo, and Fabrizio Dal Piaz. 2025. "Structural Characterization of Protein–Nucleic Acid Complexes: An Overview of the Recent Innovation in the Analytic Methods" International Journal of Molecular Sciences 26, no. 23: 11465. https://doi.org/10.3390/ijms262311465

APA Style

Bellone, M. L., Mensitieri, F., Marmo, E., Calabrese, A. N., Gaudino, G., Izzo, V., & Dal Piaz, F. (2025). Structural Characterization of Protein–Nucleic Acid Complexes: An Overview of the Recent Innovation in the Analytic Methods. International Journal of Molecular Sciences, 26(23), 11465. https://doi.org/10.3390/ijms262311465

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Structural Characterization of Protein–Nucleic Acid Complexes: An Overview of the Recent Innovation in the Analytic Methods

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