Architecture of nonspecific protein–DNA interactions in the Sso7d–DNA complex

Abstract

Many biochemical processes, including DNA packing, maintenance and control, rely on non-sequence specific protein-DNA interactions. Nonspecific DNA-binding proteins have evolved to tolerate a wide range of DNA sequences, yet bind with a respectable affinity. The nonspecific binding requirement is in contrast to that imposed on, for example, transcription factors and implies a different structural basis for the biomolecular recognition process. To address this issue, and the mechanism for archaeal DNA packing, we determined the structure of the Sso7d protein from Sulfolobus solfataricus in complex with DNA. Sso7d binds DNA by placing a triple-stranded beta-sheet across the DNA minor groove. The protein is anchored in this position by the insertion of hydrogen bond-donating side chains into the groove and additionally stabilized by electrostatic and non-polar interactions with the DNA backbone. This structure explains how strong binding can be achieved independent of DNA sequence. Sso7d binding also distorts the DNA conformation and introduces significant unwinding of the helix. This effect suggests a mechanism for DNA packing in Sulfolobus based on negative DNA supercoiling.

Crystal structure of the crenarchaeal conserved chromatin protein Cren7 and double‐stranded DNA complex

“…Two strategies of chromatin compaction in Archaea were proposed according to these findings. The genomic DNA is packaged mainly by histones in Euryarchaeota, whereas in Crenarchaeota the genomic DNA is packaged by a ''bending and unwinding'' mechanism that the genomic DNA is kinked and supercoiled by minor-groove binding proteins such as Sul7d 11 and Cren7 10 forming a compact nucleoid.…”

The recruitment of chromatin modifiers by long noncoding RNAs: lessons from PRC2

“…Although this question has yet to be experimentally established for PRC2, multiple proteins have been previously shown to bind a diverse cohort of nucleic acid partners through functional interactions. Such proteins function in DNA replication and recombination (Jensen et al 1976), DNA packaging (Agback et al 1998), RNA folding (Seraphin et al 1989;Mohr et al 2002;Huang et al 2005;Bhaskaran and Russell 2007), and RNA degradation (Chen et al 2001;Makino et al 2013). Restriction enzymes can bind noncognate sites with high affinity, often with a K d that is similar to that of their canonical site (Hinsch et al 1980;Woodhead and Malcolm 1980).…”

Enforced Presentation of an Extrahelical Guanine to the Lesion Recognition Pocket of Human 8-Oxoguanine Glycosylase, hOGG1

“…When proteins interact with DNA lacking any specific recognition feature, the two macromolecules form large ensembles of rapidly interconverting complexes, and this inherent heterogeneity has hampered attempts to characterize nonspecific protein-DNA interactions at atomic resolution (21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32). We have overcome this problem by developing a straightforward means by which to drastically limit the region a protein can explore while diffusing along DNA, through the introduction of an intermolecular disulfide cross-link (DXL) between protein and DNA.…”