Structural Insights into Nonspecific Binding of DNA by TrmBL2, an Archaeal Chromatin Protein. Issue 20 (9th October 2015)

• Record Type: Journal Article
• Authors: Ahmad, Misbha Ud Din; Waege, Ingrid; Hausner, Winfried; Thomm, Michael; Boos, Winfried; Diederichs, Kay; Welte, Wolfram
• Is Part Of: Journal of molecular biology. Volume 427:Issue 20(2015:Oct. 15)
• Page Start: 3216
• Page End: 3229
• Publication Date: 2015-10-09
• Subjects: ewHTH extended winged helix–turn–helix -- wHTH winged helix–turn–helix -- dsDNA double-stranded DNA -- NCS noncrystallographic symmetry -- HTH helix–turn–helix; TrmBL2 -- nonspecific DNA binding -- chromatin protein -- protein–DNA complex -- Archaea; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2015.08.012
• Languages: English
• ISSNs: 0022-2836

Abstract

Abstract: The crystal structure of TrmBL2 from the archaeon Pyrococcus furiosus shows an association of two pseudosymmetric dimers. The dimers follow the prototypical design of known bacterial repressors with two helix–turn–helix (HTH) domains binding to successive major grooves of the DNA. However, in TrmBL2, the two dimers are arranged at a mutual displacement of approximately 2 bp so that they associate with the DNA along the double-helical axis at an angle of approximately 80°. While the deoxyribose phosphate groups of the double-stranded DNA (dsDNA) used for co-crystallization are clearly seen in the electron density map, most of the nucleobases are averaged out. Refinement required to assume a superposition of at least three mutually displaced dsDNAs. The HTH domains interact primarily with the deoxyribose phosphate groups and polar interactions with the nucleobases are almost absent. This hitherto unseen mode of DNA binding by TrmBL2 seems to arise from nonoptimal protein–DNA contacts made by its four HTH domains resulting in a low-affinity, nonspecific binding to DNA. Graphical abstract: Highlights: The structure of an archaeal DNA binding protein alone and in complex with dsDNA. The tetrameric protein shows an as yet unknown dsDNA binding mode. The crystal structure shows a superposition of three mutually shifted copies of the bound DNA. Compared to other HTH repressor proteins, polar interactions seem to be eluded.