Electrostatic Mechanism for DNA Bending by bZIP Proteins

Paolella, David N.; Liu, Yichin; Fabian, Miles A.; Schepartz, Alanna

doi:10.1021/bi970515b

Cited by 41 publications

(53 citation statements)

References 39 publications

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“…When compared to the BamHI multimers, the CRE multimers showed large migrational anomalies that increased with multimer length, whereas the AP-1 multimers did not ( Figure 2B). These results confirm those obtained from phasing analysis (2) and ligation ladder analysis (35), as well as minicircle ligation kinetics (28) To verify that the distortion in the CRE site resulted from a unidirectional bend, as opposed to nondirectional flexibility, we examined the relative mobilities of multimers of 15 bp monomers containing the CRE or AP-1 sites (Figure 1). These CRE 15 and AP-1 15 monomers contained the CRE or AP-1 site, respectively, surrounded by flanking sequences that should not, on their own, exhibit an overall bend (2).…”

Section: Verification Of the Intrinsic Bend In The Cre Sitesupporting

confidence: 81%

“…The presence of this base pair produces a TGA step at the AP-1 ligation junction. Previous work using 21 base pair oligonucleotides lacking a C‚G base pair at the ligation junction (and the resulting TGA step) demonstrates that the AP-1 sequence exhibits little or no intrinsic curvature as detected by ligation ladder analysis (35). Subscripts (for example, CRE 1,-1 ) indicate which base pair in the sequence differed from the CRE sequence.…”

Section: Verification Of the Intrinsic Bend In The Cre Sitementioning

confidence: 99%

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Sequence Determinants of the Intrinsic Bend in the Cyclic AMP Response Element

Sloan

Schepartz

1998

Biochemistry

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The cyclic AMP response element (CRE site, ATGACGTCAT) is the DNA target for transcription factors whose activities are regulated by cyclic AMP (1). Recently, we discovered that the CRE site is bent by 10-13°toward the major groove (2). Little or no bend is detected in the related AP-1 site (ATGACTCAT), which differs from the CRE site by loss of a single, central, C‚G base pair (2, 3). Here we describe experiments designed to identify which base pairs within the CRE site induce the bent structure in an attempt to understand the origins of the dramatically different conformations of the CRE and AP-1 sites. Our data indicate that the intrinsic CRE bend results from distortion within the TGA sequence found in each CRE half site (ATGAC). These two TGA sequences are located in phase with one another in the CRE sequence but are not (completely) in phase in the AP-1 sequence. This difference in phasing leads to the overall difference in bend as detected by gel (2) and cyclization methods (S. C. Hockings, J. D. Kahn, and D. M. Crothers, unpublished results; M. A. Fabian and A. Schepartz, unpublished results). Our results confirm earlier predictions of altered structure within TG steps, provide insight into the structural reorganizations induced in DNA by bZIP proteins, and lead to a revision of the relationship between the structures of the free and bZIP-bound forms of the CRE and AP-1 sites.

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Section: Verification Of the Intrinsic Bend In The Cre Sitesupporting

confidence: 81%

Section: Verification Of the Intrinsic Bend In The Cre Sitementioning

confidence: 99%

Sequence Determinants of the Intrinsic Bend in the Cyclic AMP Response Element

Sloan

Schepartz

1998

Biochemistry

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“…Although the final stage of DNA bending and active-site assembly appears to be driven by mechanical forces generated by the protein, the initiation of bending may instead depend significantly on asymmetric phosphate charge neutralization on one face of the double helix (5,6). It is notable that the 30-aa carboxyl-terminal subdomains of EcoRV (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…DNA bending is important to histone-mediated condensation and transcriptional initiation (3,4), so that an understanding of the underlying forces generating the bend is of considerable biological significance. Asymmetric neutralization of phosphates by positively charged groups on proteins is known to be important in some cases (5,6). By this mechanism, the DNA itself plays an active role in the process of bending.…”

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confidence: 99%

Crystallographic snapshots along a protein-induced DNA-bending pathway

Horton

Perona

2000

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

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Two new high-resolution cocrystal structures of EcoRV endonuclease bound to DNA show that a large variation in DNA-bending angles is sampled in the ground state binary complex. Together with previous structures, these data reveal a contiguous series of protein conformational states delineating a specific trajectory for the induced-fit pathway. Rotation of the DNA-binding domains, together with movements of two symmetry-related helices binding in the minor groove, causes base unstacking at a key base-pair step and propagates structural changes that assemble the active sites. These structures suggest a complex mechanism for DNA bending that depends on forces generated by interacting protein segments, and on selective neutralization of phosphate charges along the inner face of the bent double helix.

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“…Fos and Jun induce opposite directions of DNA bending based on gel electrophoretic phasing analysis (5,6). The opposite directions of DNA bending are caused by the converse electrostatic interactions between Fos and Jun and the phosphodiester backbone (7)(8)(9)(10)(11)(12). No significant DNA bending was observed in the x-ray crystal structure of the bZIP domains of Fos and Jun or in cyclization or minicircle binding experiments (13,14).…”

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confidence: 99%

Molecular basis of cooperative DNA bending and oriented heterodimer binding in the NFAT1—Fos–Jun—ARRE2 complex

Diebold

Rajaram

Leonard

et al. 1998

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

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Cooperative DNA binding by transcription factors that bind to separate recognition sites is likely to require bending of intervening sequences and the appropriate orientation of transcription factor binding. We investigated DNA bending in complexes formed by the basic region-leucine zipper domains of Fos and Jun with the DNA binding region of nuclear factor of activated T cells 1 (NFAT1) at composite regulatory elements using gel electrophoretic phasing analysis. The NFAT1-Fos-Jun complex induced a bend at the ARRE2 site that was distinct from the sum of the bends induced by NFAT1 and Fos-Jun separately. We designate this difference DNA bending cooperativity. The bending cooperativity was directed toward the interaction interface between Fos-Jun and NFAT1. We also examined the influence of NFAT1 on the orientation of Fos-Jun heterodimer binding using a novel fluorescence resonance energy transfer assay. The interaction with NFAT1 could reverse the orientation of Fos-Jun heterodimer binding to the ARRE2 site. The principal determinants of both cooperative DNA bending and oriented heterodimer binding were localized to three amino acid residues at the amino-terminal ends of the leucine zippers of Fos and Jun. Consequently, interactions between transcription factors can remodel promoters by altering DNA bending and the orientation of heterodimer binding.

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Electrostatic Mechanism for DNA Bending by bZIP Proteins

Cited by 41 publications

References 39 publications

Sequence Determinants of the Intrinsic Bend in the Cyclic AMP Response Element

Sequence Determinants of the Intrinsic Bend in the Cyclic AMP Response Element

Crystallographic snapshots along a protein-induced DNA-bending pathway

Molecular basis of cooperative DNA bending and oriented heterodimer binding in the NFAT1—Fos–Jun—ARRE2 complex

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