title: Search by proteins for their DNA target site: 2. The effect of DNA conformation on the dynamics of multidomain proteins.
abstract: Multidomain transcription factors, which are especially abundant in eukaryotic genomes, are advantageous to accelerate the search kinetics for target site because they can follow the intersegment transfer via the monkey-bar mechanism in which the protein forms a bridged intermediate between two distant DNA regions. Monkey-bar dynamics highly depends on the properties of the multidomain protein (the affinity of each of the constituent domains to the DNA and the length of the linker) and the DNA molecules (their inter-distance and inter-angle). In this study, we investigate using coarse-grained molecular dynamics simulations how the local conformation of the DNA may affect the DNA search performed by a multidomain protein Pax6 in comparison to that of the isolated domains. Our results suggest that in addition to the common rotation-coupled translation along the DNA major groove, for curved DNA the tethered domains may slide in a rotation-decoupled sliding mode. Furthermore, the multidomain proteins move by longer jumps on curved DNA compared with those performed by the single domain protein. The long jumps originate from the DNA curvature bringing two sequentially distant DNA sites into close proximity with each other and they suggest that multidomain proteins may move on highly curved DNA faster than linear DNA.
authors.affiliation: Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Arnab
authors.initials: A
authors.lastname: Bhattacherjee
authors.affiliation: Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel Koby.Levy@weizmann.ac.il.
authors.forename: Yaakov
authors.initials: Y
authors.lastname: Levy
mesh_terms: D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D004270:DNA, Circular / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D005136:Eye Proteins / Q000737:chemistry / Q000378:metabolism; D018398:Homeodomain Proteins / Q000737:chemistry / Q000378:metabolism; D009690:Nucleic Acid Conformation; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*
chemical_list: D004270:DNA, Circular; D004268:DNA-Binding Proteins; D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; D014157:Transcription Factors; D004247:DNA