Investigating Cation-π Interactions in NGAL Using Single-Molecule Force Spectroscopy

Cation-π interactions are electrostatic interactions between cations and electron-rich aromatics. They play a significant role in many biological systems as important driving forces for protein folding, stability, and receptor-ligand interactions/recognition. Currently, most cation-π interactions in proteins are predicted and discovered through statistical analysis conducted by programs and theoretical calculations. Due to the lack of high-precision measurement methods for small differences, relevant experimental validation and quantitative work remain very limited.

NanjingUniversity Professor Zheng Peng’s research group utilized a high-precision detection technology based on atomic force microscopy single-molecule force spectroscopy (AFM-SMFS) to measure the stability of the neutrophil gelatinase-associated lipocalin (NGAL) protein bound to iron through cation-π interactions and the interactions between its three cationic residues and the bound catechol. Force spectroscopy measurements at two different stretching sites (C122/C133) indicate that NGAL, which binds iron through weak interactions, exhibits greater stability and dynamics. This work achieves high-precision detection of cation-π interactions in NGAL, revealing its molecular binding mechanisms and providing a novel experimental tool for understanding the commonly existing cation-π interactions in proteins.

Zheng Peng, Professor at the School of Chemistry and Chemical Engineering, Nanjing University, and PhD supervisor. He obtained his bachelor’s degree from Nanjing University in 2008 and his PhD from the University of British Columbia in Canada in 2013, subsequently conducting postdoctoral research at Harvard Medical School. He began independent work in 2015. His research mainly focuses on using single-molecule force spectroscopy to study protein folding, assembly, and interactions, with research directions including viral adhesion, membrane protein assembly, and the regulation of proteins by metals. Research group homepage: https://hysz.nju.edu.cn/pengzhenglab/.

Jingyuan Nie, Yibing Deng, Fang Tian, Shengchao Shi & Peng Zheng^*. Detection of weak non-covalent cation-π interactions in NGAL by single-molecule force spectroscopy. Nano Research https://doi.org/10.1007/s12274-021-4065-9.

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