Conformation and Dynamics of DNA and Protein-DNA Complexes by 31P NMR

Gorenstein, David G.

doi:10.1021/cr00029a007

Cited by 215 publications

(254 citation statements)

References 64 publications

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“…Thus, the coupling constants and the 31P chemical shifts both reflects the conformational variations occuring on P4 of (CA) during methylation. This further confirms the suitability of the 31P chemical-shift parameter for the detection of conformational changes in the double-helix backbone (Gorenstein, 1994;El Antri et al, 1993).…”

Section: Noe Analysissupporting

confidence: 69%

Sequence Dependent Effects of CpG Cytosine Methylation

Lefebvre

Mauffret

Antri

et al. 1995

European Journal of Biochemistry

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The impact of cytosine methylation in the central CpG step of two closely related octanucleotide duplexes d(CATCGATG), and d(CTTCGAAG), was examined by 'H-NMR and 31P-NMR experiments, and a quantitative structural analysis was performed using the NOE-derived distances, the sugar puckers and the E torsion angles. The two starting oligonucleotides displayed a B-DNA conformation with, however, significant local structure differences. Although the methylated oligonucleotides retained their B-DNA conformation, different structural and thermal stability effects were observed. The magnitude of the methylation effects was to depend on the initial conformation of the CpG site, which is governed by the nature of the dinucleotide AT or TT located on the CpG flanks. As an example of sequence dependence, the methylation of CpG entailed larger conformational variation in d(CATCGATG), than in d(CTTCGAAG),. In this study, the 'H and 31P chemical-shift parameters averred as extremely sensitive probes for detecting subtle conformational changes. Finally, our comparative results may aid our understanding of the structural and related biological effects produced by cytosine methylation in DNA.

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Section: Noe Analysissupporting

confidence: 69%

Sequence Dependent Effects of CpG Cytosine Methylation

Lefebvre

Mauffret

Antri

et al. 1995

European Journal of Biochemistry

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“…The phosphodiester backbone could be assigned by using 31 (37,38). Although nonstandard phosphodiester conformations could conceptually serve as markers for mismatch recognition, they are unlikely to drive MSH recognition/activation since we observe the B II conformation in both well and poorly recognized sequence contexts (Figs.…”

Section: Resultsmentioning

confidence: 89%

Sequence context effect for hMSH2-hMSH6 mismatch-dependent activation

Mazurek

Johnson

Germann

et al. 2009

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

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Numerous DNA mismatches and lesions activate MutS homologue (MSH) ATPase activity that is essential for mismatch repair (MMR).We have found that a mismatch embedded in a nearest-neighbor sequence context containing symmetric 3-purines (2 ؋ 3-purines) enhanced, whereas symmetric 3-pyrimidines (2 ؋ 3-pyrimidines) reduced, hMSH2-hMSH6 ATPase activation. The 3-purine/pyrimidine effect was most evident for G-containing mispairs. A similar trend pervaded mismatch binding (K D) and the melting of unbound oligonucleotides (T m; ⌬G). However, these latter measures did not accurately predict the hierarchy of MSH ATPase activation. NMR studies of imino proton lifetime, solvent accessibility, and NOE connectivity suggest that sequence contexts that provoke improved MSH-activation displayed enhanced localized DNA flexibility: a dynamic DNA signature that may account for the wide range of lesions that activate MSH functions. Both MSH and MLH/PMS proteins contain consensus ATPbinding and hydrolysis (ATPase) activities required for MMR (3)(4)(5). A wide range of DNA lesions activate the MSH ATPase, including the 8 possible DNA mismatches, small insertion/deletion loops, and numerous damaged/modified nucleotides (6-9). This broad spectrum of DNA substrates is remarkable compared with glycosylases that also recognize nucleotide mismatch/lesions but demonstrate a very narrow range of substrate specificity (for review see ref. 10). Structural analysis of MSH proteins bound to several mismatched nucleotides (11) have revealed a number of consistent features including a 45-60°DNA bend at the mismatch and the formation of an incipient clamp in which the MSH protein both grasps and interrogates the mismatch (12)(13)(14). Yet all of the MSH structures contact and interrogate the mismatch region similarly regardless of the mismatch and/or MSH-adenosine nucleotide configuration (11). These results underline the lack of any molecular basis for the extensive range of MSH recognition or the transition from smooth to bent DNA.Both thermal instability and altered DNA flexibility of the mismatched region have been suggested factors that might influence MSH recognition (15,16). The idea that altered DNA flexibility may be a determinant is based on picosecond motions inferred from NMR 13 C relaxation data, although MSH recognition and activation or MMR appears to occur in the millisecond-minute time scale (16). Nucleotide-stacking interactions serve an important role in stabilizing DNA helical structure (17) and have been used to account for the thermal stability of mismatched DNA (16,18). The energetic components that account for altered DNA thermal stability and flexibility are controversial (19,20).The type of mismatched nucleotides, lesions, and nearestneighbor nucleotides influence MSH recognition and activation (21-23). Here, we have systematically examined the effect of nearest-neighbor sequence context on hMSH2-hMSH6 mispair recognition and ATPase activation as a model for understanding the extensive range of MSH recognition/activation pr...

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“…In addition, torsion angle restraints for residues at the POU S / Sox2 interface were derived from heteronuclear 3 J couplings (18). The pattern of intramolecular NOEs within the DNA and the distribution of 31 P shifts (44) confirmed that the DNA was predominantly B-form.…”

Section: Methodsmentioning

confidence: 97%

Molecular Basis for Synergistic Transcriptional Activation by Oct1 and Sox2 Revealed from the Solution Structure of the 42-kDa Oct1·Sox2·Hoxb1-DNA Ternary Transcription Factor Complex

Williams¹,

Cai

Clore

2004

Journal of Biological Chemistry

159

173

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The Oct and Sox transcription factors control many different aspects of neural development and embryogenesis, often binding to adjacent sites on DNA, and interacting with one another through their DNA binding domains to regulate transcription synergistically. Oct proteins contain two DNA binding domains (POU S and POU HD ) connected by a flexible linker, which interact with DNA in a bipartite manner. Residual dipolar coupling measurements on the binary Oct1⅐DNA complex reveal that the two domains are characterized by distinct alignment tensors in both phage pf1 and polyethylene glycol/hexanol liquid crystalline media. We show that this difference is due to a fast microscopic dissociation/association process involving alternative binding modes for the weaker binding POU S domain in the binary complex. Upon binding of Sox2 to an adjacent site in the Hoxb1 regulatory element, all components of the ternary Oct1⅐Sox2⅐DNA complex share a single alignment tensor. Thus ternary complex formation increases the site-specific affinity of Oct1 for DNA by effectively locking the POU S domain in a single orientation on the DNA. The solution NMR structure of the ternary 42 kDa Oct1⅐Sox2⅐Hoxb1-DNA complex, determined by novel procedures based on orientational restraints from dipolar couplings and conjoined rigid body/torsion angle dynamics, reveals that Sox2 and POU S interact through a predominantly hydrophobic interface, surrounded by a ring of electrostatic interactions. These observations suggest a mechanism of combinatorial control involving direct protein-protein interactions on the DNA whereby Oct1 in conjunction with a co-interacting transcription factor provide cell-specific transcription regulation.Transcription regulation in eukaryotes involves the formation of protein-DNA complexes that can interact with and modulate the downstream transcriptional machinery (1, 2). Unlike prokaryotes that often use a single protein for this function, eukaryotes generally employ complexes of multiple proteins in what has been termed combinatorial control (2, 3). This mechanism effectively integrates many different signaling pathways to provide a more complex regulatory network based on a finite number of transcription factors. Biological and structural studies of these complexes indicate that combinatorial control is achieved by employing transcription factors with adaptable DNA and protein binding surfaces. This adaptability allows different combinations of these factors to interact on specific promoter elements to drive synergistic transcription regulation (2, 3).Transcription regulation by the Oct and Sox families of transcription factors reflects many of the principles of combinatorial control. Different members of each family have been shown to interact on different promoter elements to regulate transcription during embryogenesis and neural development (4, 5). The Sox family is characterized by an HMG-box DNA binding domain that binds in the minor groove, bends DNA (50 -90°) and specifically recognizes variations of the consensus...

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Conformation and Dynamics of DNA and Protein-DNA Complexes by 31P NMR

Cited by 215 publications

References 64 publications

Sequence Dependent Effects of CpG Cytosine Methylation

Sequence Dependent Effects of CpG Cytosine Methylation

Sequence context effect for hMSH2-hMSH6 mismatch-dependent activation

Molecular Basis for Synergistic Transcriptional Activation by Oct1 and Sox2 Revealed from the Solution Structure of the 42-kDa Oct1·Sox2·Hoxb1-DNA Ternary Transcription Factor Complex

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