Work

Single-molecule techniques for probing the conformation, dynamics, and interactions of intrinsically disordered proteins

Year: 2025

Type: article

Abstract: Intrinsically disordered proteins (IDPs) rely on inherent conformational dynamics to support vital cellular functions such as signaling and regulation. The heterogeneity of the conformational ensembles of IDPs poses a major challenge for classical biophysical techniques such as NMR, SAXS, and CD, which measure ensemble-averaged properties and are unable to resolve the full range of substates sampled by IDPs or their interconversions. To address these limitations of ensemble-based methods, single-molecule techniques are essential to resolve the conformational heterogeneity and dynamics by continuously monitoring various properties of individual IDPs. In this review, we focus on the most commonly employed single-molecule techniques, briefly describe their methodologies, and highlight recent developments and applications of each technique towards the study of IDP structure, dynamics and interactions.

Source: Biophysics Reviews

DOI: 10.1063/5.0287565

Authors: David DeCoeur, Min Chen, Jianhan Chen

Institution: University of Massachusetts Amherst

Language: English

Topic: Protein Structure and Dynamics

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funders: National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, Division of Chemistry

Awards: G1979993508, G3136763675, Disordered Proteins and Dynamic Interactions in Biology and Diseases., Probing Functional States and Inhibition of Flaviviral Proteases Using Nanopore Tweezers