Structure of a Complex of Tandem HMG Boxes and DNA

Stott, Katherine; Tang, George S.F.; Lee, Keng-Boon; Thomas, Jean O.

doi:10.1016/j.jmb.2006.04.059

Cited by 114 publications

(139 citation statements)

References 66 publications

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“…S1D). In this regard, previous reports have shown that one HMGB1 molecule covers 15-18 bp of DNA (32,33), which corroborates our findings that affinity markedly decreased as the ODNs became shorter than 20 nucleotides (Fig. 1C and Fig.…”

Section: Discussionsupporting

confidence: 93%

Suppression of immune responses by nonimmunogenic oligodeoxynucleotides with high affinity for high-mobility group box proteins (HMGBs)

Yanai

Chiba

Ban

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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The activation of innate immune responses by nucleic acids is central to the generation of host responses against pathogens; however, nucleic acids can also trigger the development and/or exacerbation of pathogenic responses such as autoimmunity. We previously demonstrated that the selective activation of nucleic acid-sensing cytosolic and Toll-like receptors is contingent on the promiscuous sensing of nucleic acids by high-mobility group box proteins (HMGBs). From this, we reasoned that nonimmunogenic nucleotides with high-affinity HMGB binding may function as suppressing agents for HMGB-mediated diseases, particularly those initiated and/or exacerbated by nucleic acids. Here we characterize an array of HMGB-binding, nonimmunogenic oligodeoxynucleotides (niODNs). Interestingly, we find that binding affinity is rather independent of nucleotide sequence, but is instead dependent on length and structure of the deoxyribose backbone. We further show that these ni-ODNs can strongly suppress the activation of innate immune responses induced by both classes of nucleic acid-sensing receptors. We also provide evidence for the suppressive effect of an ni-ODN, termed ISM ODN, on the induction of adaptive immune responses and in mouse models of sepsis and autoimmunity. We discuss our findings in relation to the critical role of HMGBs in initiating immune responses and the possible use of these ni-ODNs in therapeutic interventions.

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Section: Discussionsupporting

confidence: 93%

Suppression of immune responses by nonimmunogenic oligodeoxynucleotides with high affinity for high-mobility group box proteins (HMGBs)

Yanai

Chiba

Ban

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…The sequence of human TFAM (hTFAM) without the mitochondrial targeting peptide, comprising residues 43 to 246 was used for structure prediction by Phyre (38) and I-Tasser (39). Structural similarity was found to the NMR structure of the hybrid protein SRY.B derived from human SRY and rat HMGB1 (PDB accession code 2GZK; E-value 1.9 × 10 −17 ), which contains two tandem HMG boxes bound to a double stranded DNA sequence of 16 bp (40). In addition, the sequence of the intramitochondrial form of human TFAM was sent to the structure prediction server I-Tasser (39), which calculated a complete model with a confidence score of −0.99.…”

Section: Methodsmentioning

confidence: 88%

Super-resolution microscopy reveals that mammalian mitochondrial nucleoids have a uniform size and frequently contain a single copy of mtDNA

Kukat

Wurm

Spåhr

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

481

430

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Mammalian mtDNA is packaged in DNA-protein complexes denoted mitochondrial nucleoids. The organization of the nucleoid is a very fundamental question in mitochondrial biology and will determine tissue segregation and transmission of mtDNA. We have used a combination of stimulated emission depletion microscopy, enabling a resolution well below the diffraction barrier, and molecular biology to study nucleoids in a panel of mammalian tissue culture cells. We report that the nucleoids labeled with antibodies against DNA, mitochondrial transcription factor A (TFAM), or incorporated BrdU, have a defined, uniform mean size of approximately 100 nm in mammals. Interestingly, the nucleoid frequently contains only a single copy of mtDNA (average approximately 1.4 mtDNA molecules per nucleoid). Furthermore, we show by molecular modeling and volume calculations that TFAM is a main constituent of the nucleoid, besides mtDNA. These fundamental insights into the organization of mtDNA have broad implications for understanding mitochondrial dysfunction in disease and aging

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“…5B). The bends induced by either domain likely reinforce each other (109,110). For HMGB1, acetylation of lysine residues in the box A domain occurs in vivo, and it has been reported that substitution of these lysine residues compromises the preferred binding to both four-way junction DNA and constrained minicircles (107).…”

Section: High Mobility Group Proteinsmentioning

confidence: 98%

Yeast HMO1: Linker Histone Reinvented

Panday

Grove

2017

Microbiol Mol Biol Rev

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SUMMARY Eukaryotic genomes are packaged in chromatin. The higher-order organization of nucleosome core particles is controlled by the association of the intervening linker DNA with either the linker histone H1 or high mobility group box (HMGB) proteins. While H1 is thought to stabilize the nucleosome by preventing DNA unwrapping, the DNA bending imposed by HMGB may propagate to the nucleosome to destabilize chromatin. For metazoan H1, chromatin compaction requires its lysine-rich C-terminal domain, a domain that is buried between globular domains in the previously characterized yeast Saccharomyces cerevisiae linker histone Hho1p. Here, we discuss the functions of S. cerevisiae HMO1, an HMGB family protein unique in containing a terminal lysine-rich domain and in stabilizing genomic DNA. On ribosomal DNA (rDNA) and genes encoding ribosomal proteins, HMO1 appears to exert its role primarily by stabilizing nucleosome-free regions or “fragile” nucleosomes. During replication, HMO1 likewise appears to ensure low nucleosome density at DNA junctions associated with the DNA damage response or the need for topoisomerases to resolve catenanes. Notably, HMO1 shares with the mammalian linker histone H1 the ability to stabilize chromatin, as evidenced by the absence of HMO1 creating a more dynamic chromatin environment that is more sensitive to nuclease digestion and in which chromatin-remodeling events associated with DNA double-strand break repair occur faster; such chromatin stabilization requires the lysine-rich extension of HMO1. Thus, HMO1 appears to have evolved a unique linker histone-like function involving the ability to stabilize both conventional nucleosome arrays as well as DNA regions characterized by low nucleosome density or the presence of noncanonical nucleosomes.

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Structure of a Complex of Tandem HMG Boxes and DNA

Cited by 114 publications

References 66 publications

Suppression of immune responses by nonimmunogenic oligodeoxynucleotides with high affinity for high-mobility group box proteins (HMGBs)

Suppression of immune responses by nonimmunogenic oligodeoxynucleotides with high affinity for high-mobility group box proteins (HMGBs)

Super-resolution microscopy reveals that mammalian mitochondrial nucleoids have a uniform size and frequently contain a single copy of mtDNA

Yeast HMO1: Linker Histone Reinvented

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