ArticleBiophysical journal2010
Facilitated DNA search by multidomain transcription factors: cross talk via a flexible linker.
Article in Biophysical journal, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed.
- Coupled Heterogeneity to Dimeric Site-Specific Binding by the POU-Family Transcription Factor OCT2.The journal of physical chemistry. B · 2025Article
- Dynamics in Cre-loxP site-specific recombination.Current opinion in structural biology · 2024Review
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- Skipping events impose repeated binding attempts: profound kinetic implications of protein-DNA conformational changes.Nucleic acids research · 2024Article
- Cooperativity boosts affinity and specificity of proteins with multiple RNA-binding domains.NAR genomics and bioinformatics · 2023Article
- Nucleosome breathing facilitates cooperative binding of pluripotency factors Sox2 and Oct4 to DNA.Biophysical journal · 2022Article
- Overview of theBiophysical reviews · 2021Article
- What Are the Molecular Requirements for Protein Sliding along DNA?The journal of physical chemistry. B · 2021Article
- Contrasting DNA-binding behaviour by ISL1 and LHX3 underpins differential gene targeting in neuronal cell specification.Journal of structural biology: X · 2021Article
- Prerecognition Diffusion Mechanism of Human DNA Mismatch Repair Proteins along DNA: Msh2-Msh3 versus Msh2-Msh6.Biochemistry · 2020Article
- Protein Diffusion on Charged Biopolymers: DNA versus Microtubule.Biophysical journal · 2020Article
- Probing the Conformational Changes Associated with DNA Binding to PARP1.Biochemistry · 2020Article
- Balance between asymmetry and abundance in multi-domain DNA-binding proteins may regulate the kinetics of their binding to DNA.PLoS computational biology · 2020Article
- Quantifying the two-state facilitated diffusion model of protein-DNA interactions.Nucleic acids research · 2019Article
- Mitotic chromosome binding predicts transcription factor properties in interphase.Nature communications · 2019Article
- Plasticity in oligomerization, operator architecture, and DNA binding in the mode of action of a bacterial BThe Journal of biological chemistry · 2018Article
- Article
- Diffusion of ring-shaped proteins along DNA: case study of sliding clamps.Nucleic acids research · 2018Article
- Searching target sites on DNA by proteins: Role of DNA dynamics under confinement.Nucleic acids research · 2015Article
- Balancing between affinity and speed in target DNA search by zinc-finger proteins via modulation of dynamic conformational ensemble.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
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3 authors.
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No grant is acknowledged in the PubMed record.
Abstract
More than 70% of eukaryotic proteins are composed of multiple domains. However, most studies of the search for DNA focus on individual protein domains and do not consider potential cross talk within a multidomain transcription factor. In this study, the molecular features of the DNA search mechanism were explored for two multidomain transcription factors: human Pax6 and Oct-1. Using a simple computational model, we compared a DNA search of multidomain proteins with a search of isolated domains. Furthermore, we studied how manipulating the binding affinity of a single domain to DNA can affect the overall DNA search of the multidomain protein. Tethering the two domains via a flexible linker increases their affinity to the DNA, resulting in a higher propensity for sliding along the DNA, which is more significant for the domain with the weaker DNA-binding affinity. In this case, the domain that binds DNA more tightly anchors the multidomain protein to the DNA and, via the linker, increases the local concentration of the weak DNA-binding domain (DBD). The tethered domains directly exchange between two parallel DNA molecules via a bridged intermediate, where intersegmental transfer is promoted by the weaker DBD. We found that, in general, the relative affinity of the two domains can significantly affect the cross talk between them and thus their overall capability to search DNA efficiently. The results we obtained by examining various multidomain DNA-binding proteins support the necessity of discrepancies between the DNA-binding affinities of the constituent domains.
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