Crystal structure of the specific DNA-binding domain of Tc3 transposase of C.elegans in complex with transposon DNA

Pouderoyen, Gertie van; Ketting, René F.; Perrakis, Anastassis; Plasterk, Ronald H.A.; Sixma, Titia K.

doi:10.1093/emboj/16.19.6044

Cited by 99 publications

(79 citation statements)

References 72 publications

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“…The observed DNA transformations [21,23] are in agreement with the results of the present modelling. As in experiment, in our theory the static excitation for the DNA with equivalent states has the form of a kink (24) -the transition between the conformations of the double helix and has maximum macromolecule deformation at the center of the A-B junction (Figure 4).…”

Section: Static Excitation In the Macromolecule With Equivalent Statesupporting

confidence: 91%

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Modeling B–A Transformations of the DNA Double Helix

Волков

2005

J Biol Phys

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Abstract. An approach to the description of DNA conformational transformations of B-A type is presented. Due to the consideration of joint motions of DNA structural elements the model for DNA transformation is constructed in the two-component form. One component is the degree of freedom of the elastic rod, and another component -the effective coordinate of the conformational transformation. In the model the internal and external components are interrelated, as it is characteristic for DNA B-A rearrangements. It is demonstrated that kinetic energy of the double helix transformations of heterogeneous DNA can be put in homogeneous form. In the frame of the developed approach the possible localized excitations in a static state are found to compare with the experiments on DNA B-A deformability. The comparison shows good qualitative agreement between theory and experiment. The conclusion is made that the found excitations in the DNA structure may be classified as static conformational solitons, and that such localized excitations may play the key role in the mechanisms of DNA intrinsic bending.

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Section: Static Excitation In the Macromolecule With Equivalent Statesupporting

confidence: 91%

“…These results may be compared with the data of molecular images of the A-B transformation in the DNA-protein complex [23]. In the complex the protein is attached to one part of the DNA fragment and another part is free.…”

Section: Static Excitation In the Macromolecule With Equivalent Statementioning

confidence: 99%

Modeling B–A Transformations of the DNA Double Helix

Волков

2005

J Biol Phys

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“…The first of these HTH motifs has been crystallized in complex with double-stranded DNA corresponding to the termini of Tc3 transposons in Caenorhabditis elegans (12). The crystal structure indeed showed a HTH fold, and a dimer of transposase subunits bringing together the two DNA ends.…”

Section: The Transposase the Dna-binding Domainmentioning

confidence: 99%

Sleeping Beauty Transposition

Ivics

Izsvák

2015

Microbiol Spectr

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Sleeping Beauty (SB) is a synthetic transposon that was constructed based on sequences of transpositionally inactive elements isolated from fish genomes. SB is a Tc1/mariner superfamily transposon following a cut-and-paste transpositional reaction, during which the element-encoded transposase interacts with its binding sites in the terminal inverted repeats of the transposon, promotes the assembly of a synaptic complex, catalyzes excision of the element out of its donor site, and integrates the excised transposon into a new location in target DNA. SB transposition is dependent on cellular host factors. Transcriptional control of transposase expression is regulated by the HMG2L1 transcription factor. Synaptic complex assembly is promoted by the HMGB1 protein and regulated by chromatin structure. SB transposition is highly dependent on the nonhomologous end joining (NHEJ) pathway of double-strand DNA break repair that generates a transposon footprint at the excision site. Through its association with the Miz-1 transcription factor, the SB transposase downregulates cyclin D1 expression that results in a slowdown of the cell-cycle in the G1 phase, where NHEJ is preferentially active. Transposon integration occurs at TA dinucleotides in the target DNA, which are duplicated at the flanks of the integrated transposon.

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“…Such elements share a common mechanism of integration with retroviruses, and the catalytic domains of ASV and HIV integrases are highly homologous to those of Mu, Tn5, and Tc3 transposases (39 -43). The Tc3 transposase is a 329-amino acid protein with an N-terminal DNA binding domain, a discreet second DNA binding domain flanking the N-terminal domain, and a catalytic core domain with a DDE motif (44). For the following study, we developed a structural model for HIV-1 IN with bound LTR DNA ends.…”

Section: Hiv-1mentioning

confidence: 99%

“…1 shows our structural model for HIV-1 integrase. We assembled the three functional domains of integrase into an integrated structure by superimposing the separate two-domain crystal structures for integrase: the N-terminal domain and catalytic core (PDB code 1K6Y (44,49,59)) and the catalytic core and C-terminal domain (1EX4 (50)) (Fig. 1A).…”

Section: Structural Model Of Hiv-1 In With Ltr Dna-although a Crystalmentioning

confidence: 99%

Identification of Amino Acids in HIV-1 and Avian Sarcoma Virus Integrase Subsites Required for Specific Recognition of the Long Terminal Repeat Ends

Chen

Weber

Harrison

et al. 2006

Journal of Biological Chemistry

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A tetramer model for HIV-1 integrase (IN) with DNA representing 20 bp of the U3 and U5 long terminal repeats (LTR) termini was assembled using structural and biochemical data and molecular dynamics simulations. It predicted amino acid residues on the enzyme surface that can interact with the LTR termini. A separate structural alignment of HIV-1, simian sarcoma virus (SIV), and avian sarcoma virus (ASV) INs predicted which of these residues were unique. To determine whether these residues were responsible for specific recognition of the LTR termini, the amino acids from ASV IN were substituted into the structurally equivalent HIV-12 DNA integration is a concerted process that occurs in defined stages. After assembly of a stable complex of the viral integrase (IN) and host cell proteins with specific DNA sequences at the end of the HIV-1 LTR, the terminal dinucleotides are removed from each 3Ј end by endonucleolytic processing. The viral DNA 3Ј ends are then covalently linked to the host cell target DNA in a concerted reaction. Biochemical details concerning the processing and joining steps in the integration process have been reported for several retroviruses including avian sarcomaleukosis virus (ASV), murine leukemia virus (MuLV), and HIV-1. Specific DNA sequences at the 3Ј end of the viral LTR are required for recognition by the assembled viral integrase complex. Typically, the terminal 12-20 nucleotides are sufficient. After 3Ј processing of the CAXX sequence from the ends, viral DNA ends are joined by the viral integrase and the gapped intermediates are repaired, and unpaired viral 5Ј ends are excised by host nucleases. This results in a 4 -6-base pair duplication of host cell DNA, depending upon the virus, flanking the integrated viral DNA. Both the 3Ј processing and viral DNA-host DNA joining steps require integrase to be assembled on the specific viral DNA substrate. Integration of viral into host DNA occurs with limited sequence specificity (1). Several cell proteins have been reported to affect the integration process (2-8).Much of the information available concerning the molecular mechanism of integration comes from the use of reconstituted systems employing duplex oligodeoxyribonucleotides (oligos). The ASV IN, for example, catalyzes specific cleavage at the 3Ј end of the strands adjacent to the conserved CA dinucleotide using 15-bp substrates corresponding to the ASV U3 or U5 termini (9, 10). Similar substrates were used to demonstrate the joining reaction in which one oligo integrated into another (11-12). For HIV-1 duplex oligo substrates of comparable size, selected nucleotide substitutions in the U5 and U3 LTR regions were shown to affect one or both of the catalytic functions of HIV-1 integrase. Nucleic acid substitutions in the HIV-1 U5 LTR region, for example, can inhibit 3Ј processing (e.g. positions 1-5 and 9 -11) or not (e.g. positions 6 -8 and 12-14) (13). Other changes at specific nucleic acid positions in the HIV-1 U3 and U5 LTR regions can affect each of the catalytic reactions, althou...

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Crystal structure of the specific DNA-binding domain of Tc3 transposase of C.elegans in complex with transposon DNA

Cited by 99 publications

References 72 publications

Modeling B–A Transformations of the DNA Double Helix

Modeling B–A Transformations of the DNA Double Helix

Sleeping Beauty Transposition

Identification of Amino Acids in HIV-1 and Avian Sarcoma Virus Integrase Subsites Required for Specific Recognition of the Long Terminal Repeat Ends

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