biostudies-literatureHaußermann KEuropean Research CouncilDeutsche Forschungsgemeinschaft7662-7667https://www.ebi.ac.uk/biostudies/studies/S-EPMC6986896biostudies-literatureUnknown58(23)Protein-protein and protein-substrate interactions are critical to function and often depend on factors that are difficult to disentangle. Herein, a combined biochemical and biophysical approach, based on electrically switchable DNA biochips and single-molecule mass analysis, was used to characterize the DNA binding and protein oligomerization of the transcription factor, forkhead box protein P2 (FOXP2). FOXP2 contains domains commonly involved in nucleic-acid binding and protein oligomerization, such as a C₂ H₂ -zinc finger (ZF), and a leucine zipper (LZ), whose roles in FOXP2 remain largely unknown. We found that the LZ mediates FOXP2 dimerization via coiled-coil formation but also contributes to DNA binding. The ZF contributes to protein dimerization when the LZ coAngewandte Chemie (International ed. in English)Dissecting FOXP2 Oligomerization and DNA Binding.PMC6986896Leibniz Program724261SFB863 TP A9Starting Grant #337757 (to PK)Consolidator Grant #724261 (to HD)337757256270Dietz HYoung GHaußermann KKukura PfalseDissecting FOXP2 Oligomerization and DNA Binding.Protein-protein and protein-substrate interactions are critical to function and often depend on factors that are difficult to disentangle. Herein, a combined biochemical and biophysical approach, based on electrically switchable DNA biochips and single-molecule mass analysis, was used to characterize the DNA binding and protein oligomerization of the transcription factor, forkhead box protein P2 (FOXP2). FOXP2 contains domains commonly involved in nucleic-acid binding and protein oligomerization, such as a C₂ H₂ -zinc finger (ZF), and a leucine zipper (LZ), whose roles in FOXP2 remain largely unknown. We found that the LZ mediates FOXP2 dimerization via coiled-coil formation but also contributes to DNA binding. The ZF contributes to protein dimerization when the LZ co2019-01-01T00:00:00Z2019 Jun2026-05-06T21:25:49.874Z2020-05-22T10:49:13ZS-EPMC69868963088762210.1002/anie.201901734