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Journal ArticleDOI

Structure of catabolite gene activator protein at 2.9 Å resolution suggests binding to left-handed B-DNA

30 Apr 1981-Nature (Nature)-Vol. 290, Iss: 5809, pp 744-749
TL;DR: The 2.9 Å resolution crystal structure of Escherichia coli catabolite gene activator protein (CAP) completed with cyclic AMP reveals two distinct structural domains separated by a cleft, suggesting that the CAP conversion of right- to left-handed DNA in a closed supercoil, is what activates transcription by RNA polymerase.
Abstract: The 2.9 A resolution crystal structure of Escherichia coli catabolite gene activator protein (CAP) complexed with cyclic AMP reveals two distinct structural domains separated by a cleft. The smaller carboxy-terminal domain is presumed to bind DNA while the amino-terminal domain is seen to bind cyclic AMP. Model building studies suggest that CAP binds to left-handed B-type DNA, contracting its major groove via two alpha-helices. It is possible that the CAP conversion of right- to left-handed DNA in a closed supercoil, is what activates transcription by RNA polymerase.
Citations
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Journal ArticleDOI
24 Jun 1988-Science
TL;DR: A 30-amino-acid segment of C/EBP, a newly discovered enhancer binding protein, shares notable sequence similarity with a segment of the cellular Myc transforming protein, and may represent a characteristic property of a new category of DNA binding proteins.
Abstract: A 30-amino-acid segment of C/EBP, a newly discovered enhancer binding protein, shares notable sequence similarity with a segment of the cellular Myc transforming protein. Display of these respective amino acid sequences on an idealized alpha helix revealed a periodic repetition of leucine residues at every seventh position over a distance covering eight helical turns. The periodic array of at least four leucines was also noted in the sequences of the Fos and Jun transforming proteins, as well as that of the yeast gene regulatory protein, GCN4. The polypeptide segments containing these periodic arrays of leucine residues are proposed to exist in an alpha-helical conformation, and the leucine side chains extending from one alpha helix interdigitate with those displayed from a similar alpha helix of a second polypeptide, facilitating dimerization. This hypothetical structure is referred to as the "leucine zipper," and it may represent a characteristic property of a new category of DNA binding proteins.

3,256 citations

Journal ArticleDOI
26 Jun 1992-Science
TL;DR: A 3.5 angstrom resolution electron density map of the HIV-1 reverse transcriptase heterodimer complexed with nevirapine, a drug with potential for treatment of AIDS, reveals an asymmetric dimer.
Abstract: A 3.5 angstrom resolution electron density map of the HIV-1 reverse transcriptase heterodimer complexed with nevirapine, a drug with potential for treatment of AIDS, reveals an asymmetric dimer. The polymerase (pol) domain of the 66-kilodalton subunit has a large cleft analogous to that of the Klenow fragment of Escherichia coli DNA polymerase I. However, the 51-kilodalton subunit of identical sequence has no such cleft because the four subdomains of the pol domain occupy completely different relative positions. Two of the four pol subdomains appear to be structurally related to subdomains of the Klenow fragment, including one containing the catalytic site. The subdomain that appears likely to bind the template strand at the pol active site has a different structure in the two polymerases. Duplex A-form RNA-DNA hybrid can be model-built into the cleft that runs between the ribonuclease H and pol active sites. Nevirapine is almost completely buried in a pocket near but not overlapping with the pol active site. Residues whose mutation results in drug resistance have been approximately located.

1,902 citations

Journal ArticleDOI
TL;DR: The structures of more than 20 proteins containing coiled-coil domains have been solved to high resolution and provided many new insights into the structure of coiled coils, their discontinuities, their relationship with other helical bundles and the problems connected with their prediction from protein sequences.

1,279 citations

Journal ArticleDOI
01 Apr 1984-Nature
TL;DR: The bending locus of trypanosome kinetoplast DNA, identified by gel electrophoresis, has tracts of a simple repeat sequence symmetrically distributed about it, with a repeat interval of 10 base pairs.
Abstract: The bending locus of trypanosome kinetoplast DNA, identified by gel electrophoresis, has tracts of a simple repeat sequence (CA5–6 T) symmetrically distributed about it, with a repeat interval of 10 base pairs The analogous bending induced when catabolite gene activating protein binds to its recognition sequence near the promoter of the Escherichia coli lac operon is centred on a site about 5–7 base pairs away from the centre of the protein binding site

1,271 citations

Journal ArticleDOI
TL;DR: CNG channels are nonselective cation channels that do not discriminate well between alkali ions and even pass divalent cations, in particular Ca2+.
Abstract: Cyclic nucleotide-gated (CNG) channels are nonselective cation channels first identified in retinal photoreceptors and olfactory sensory neurons (OSNs). They are opened by the direct binding of cyclic nucleotides, cAMP and cGMP. Although their activity shows very little voltage dependence, CNG channels belong to the superfamily of voltage-gated ion channels. Like their cousins the voltage-gated K+ channels, CNG channels form heterotetrameric complexes consisting of two or three different types of subunits. Six different genes encoding CNG channels, four A subunits (A1 to A4) and two B subunits (B1 and B3), give rise to three different channels in rod and cone photoreceptors and in OSNs. Important functional features of these channels, i.e., ligand sensitivity and selectivity, ion permeation, and gating, are determined by the subunit composition of the respective channel complex. The function of CNG channels has been firmly established in retinal photoreceptors and in OSNs. Studies on their presence in other sensory and nonsensory cells have produced mixed results, and their purported roles in neuronal pathfinding or synaptic plasticity are not as well understood as their role in sensory neurons. Similarly, the function of invertebrate homologs found in Caenorhabditis elegans, Drosophila, and Limulus is largely unknown, except for two subunits of C. elegans that play a role in chemosensation. CNG channels are nonselective cation channels that do not discriminate well between alkali ions and even pass divalent cations, in particular Ca2+. Ca2+ entry through CNG channels is important for both excitation and adaptation of sensory cells. CNG channel activity is modulated by Ca2+/calmodulin and by phosphorylation. Other factors may also be involved in channel regulation. Mutations in CNG channel genes give rise to retinal degeneration and color blindness. In particular, mutations in the A and B subunits of the CNG channel expressed in human cones cause various forms of complete and incomplete achromatopsia.

1,159 citations


Cites background from "Structure of catabolite gene activa..."

  • ...The three-dimensional structure of CAP has been determined by X-ray crystallography (265)....

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References
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Journal ArticleDOI
29 Jan 1981-Nature
TL;DR: The haemagglutinin glycoprotein of influenza virus is a trimer comprising two structurally distinct regions: a triple-stranded coiled-coil of α-helices extends 76 Å from the membrane and a globular region of antiparallel β-sheet is positioned on top of this stem.
Abstract: The haemagglutinin glycoprotein of influenza virus is a trimer comprising two structurally distinct regions: a triple-stranded coiled-coil of alpha-helices extends 76 A from the membrane and a globular region of antiparallel beta-sheet, which contains the receptor binding site and the variable antigenic determinants, is positioned on top of this stem. Each subunit has an unusual loop-like topology, starting at the membrane, extending 135 A distally and folding back to enter the membrane.

2,444 citations

Journal ArticleDOI
13 Dec 1979-Nature
TL;DR: The DNA fragment d(CpGpCpC pGp CpG pG) crystallises as a left-handed double helical molecule with Watson–Crick base pairs and an antiparallel organisation of the sugar phosphate chains.
Abstract: The DNA fragment d(CpGpCpGpCpG) crystallises as a left-handed double helical molecule with Watson-Crick base pairs and an antiparallel organisation of the sugar phosphate chains. The helix has two nucleotides in the asymmetric unit and contains twelve base pairs per turn. It differs significantly from right-handed B-DNA.

1,773 citations

Journal ArticleDOI
TL;DR: The molecular structures presented have the most probable values of bond-lengths, bond-angles and furanose ring conformations as defined by accurate X-ray crystallographic analyses of relevant monomers.

895 citations

Journal ArticleDOI
TL;DR: This chapter discusses a study analyzing the three-dimensional structure of immunoglobulins, in which the periodicity of the crystal was used to reduce the background noise and reveal the molecular outline.
Abstract: Publisher Summary This chapter discusses a study analyzing the three-dimensional structure of immunoglobulins. Heavy atom derivatives were obtained. The compounds used were (1) p -chloromercuribenzene sulfonate (PCMBS), (2) mercuric cyanide Hg(CN) 2 , and (3) chloroplatinate ion, (PtCl 6 −− ). X-ray diffraction data were measured for the native crystals and each of the heavy atom derivatives to a Bragg spacing of 6 A. Electron micrographs were prepared of sections of the Dob crystals, cut perpendicular to the short c axis. The crystals were fixed with glutaraldehyde, washed, postfixed in osmium tetroxide, and embedded in Maraglas prior to sectioning. The sections were further stained with uranyl acetate and lead citrate solutions. The method of optical integration was applied in which the periodicity of the crystal was used to reduce the background noise and reveal the molecular outline. An electron density map was calculated with phases obtained from the heavy atom derivatives. The examination of the map showed that one pair of asymmetric units (containing one complete molecule) had density corresponding to three globular regions. One region lay on the twofold axis relating the two halves of the Dob molecule.

733 citations

Journal ArticleDOI
01 Nov 1978-Nature
TL;DR: The polypeptide chain of a TBSV subunit folds into two domains, connected by a hinge, and a flexibly-linked N-terminal arm, and RNA is also not uniquely fixed to sites on the major domains.
Abstract: The polypeptide chain of a TBSV subunit folds into two domains, connected by a hinge, and a flexibly-linked N-terminal arm. Sixty of the 180 N-terminal arms inter-digitate in groups of three, in an unexpected mode of protein association. The remaining 120 arms are not uniquely positioned with respect to the rest of the subunit. RNA is also not uniquely fixed to sites on the major domains.

654 citations