The Closed Structure of an Archaeal DNA Ligase from Pyrococcus furiosus

Nishida, Hirokazu; Kiyonari, Shinichi; Ishino, Yuji; Morikawa, Kosuke

doi:10.1016/j.jmb.2006.05.062

Cited by 59 publications

(68 citation statements)

References 30 publications

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“…Consistently, the orientations of the OBD were strikingly different among the 3 crystals, suggesting the high mobility of this domain (4)(5)(6). This unfixed location of the OBD was also highlighted from the crystal structures of smaller ATPdependent DNA ligases (23,24), which exhibited OBD orientations, not only different from our structure, but also from each other.…”

Section: Resultssupporting

confidence: 83%

“…S3A). This improvement of the docking procedure seems to be reasonable, considering that a 25°kink motion in the DBD was observed between the PfuLig and hLigI crystal structures (4,6).…”

Section: Resultsmentioning

confidence: 54%

“…The DNA-free PfuLig and hLigI in complex with DNA adopted the closed conformations, and both exhibited interactions between the N-terminal DBD and the C-terminal OBD. However, even these 2 closed conformations exhibited the pivot motion of OBD by nearly 180° (4,6). In contrast to the OBD, the orientations between DBD and AdD were similar among the 3 crystals.…”

Section: Resultsmentioning

confidence: 93%

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Mechanism of replication machinery assembly as revealed by the DNA ligase–PCNA–DNA complex architecture

Mayanagi

Kiyonari

Saito

et al. 2009

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

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The 3D structure of the ternary complex, consisting of DNA ligase, the proliferating cell nuclear antigen (PCNA) clamp, and DNA, was investigated by single-particle analysis. This report presents the structural view, where the crescent-shaped DNA ligase with 3 distinct domains surrounds the central DNA duplex, encircled by the closed PCNA ring, thus forming a double-layer structure with dual contacts between the 2 proteins. The relative orientations of the DNA ligase domains, which remarkably differ from those of the known crystal structures, suggest that a large domain rearrangement occurs upon ternary complex formation. A second contact was found between the PCNA ring and the middle adenylation domain of the DNA ligase. Notably, the map revealed a substantial DNA tilt from the PCNA ring axis. This structure allows us to propose a switching mechanism for the replication factors operating on the PCNA ring.DNA replication ͉ electron microscopy ͉ single-particle analysis ͉ DNA sliding clamp ͉ protein-DNA complex D NA ligase plays essential roles in various DNA transactions, such as joining Okazaki fragments in DNA replication and nick-sealing at the final step of several DNA repair pathways, including nucleotide excision repair, base excision repair, and mismatch repair (1, 2). The enzyme catalyzes phosphodiester bond formation at the nicks generated within dsDNA, through the well-conserved 3-step reaction using either NAD ϩ or ATP as a cofactor (3). At the first step, the DNA ligase interacts with the nucleotide cofactor to form a covalent ligase-nucleoside monophosphate. At the second step, the bound AMP is transferred to the 5Ј terminus of the DNA, and finally, a phosphodiester bond is formed by a reaction between the 5Ј-DNAadenylate and the 3Ј-hydroxy group.To date, 3 crystal structures of ATP-dependent eukaryotictype DNA ligases have been reported. The structures of the 2 archaeal DNA ligases from Pyrococcus furiosus (PfuLig) and Sulfolobus solfataricus (SsoLig) were determined in the closed (4) and extended forms (5), respectively. The structure of the human DNA ligase 1 (hLigI) in complex with DNA (6) revealed that the enzyme entirely encircles the nicked DNA. All of these DNA ligases are in common composed of 3 domains, designated as the DNA binding domain (DBD), the adenylation domain (AdD), and the OB-fold domain (OBD), in the sequences from the N to C termini. Although the internal architectures of these domains are strikingly similar among the 3 DNA ligases, their relative domain orientations within each enzyme are quite different. Similar to many other replication factors, such as DNA polymerase and Flap endonuclease 1 (FEN1), DNA ligases exhibit the full activity by binding to proliferating cell nuclear antigen (PCNA). A small-angle X-ray scattering analysis revealed that the morphology of SsoLig in complex with PCNA coincides with the extended structure of SsoLig alone (5). However, the structure of the ternary Lig-PCNA-DNA complex remains unknown.PCNA interacts with various protein factors to contr...

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Section: Resultssupporting

confidence: 83%

“…S3A). This improvement of the docking procedure seems to be reasonable, considering that a 25°kink motion in the DBD was observed between the PfuLig and hLigI crystal structures (4,6).…”

Section: Resultsmentioning

confidence: 54%

Section: Resultsmentioning

confidence: 93%

See 1 more Smart Citation

Mechanism of replication machinery assembly as revealed by the DNA ligase–PCNA–DNA complex architecture

Mayanagi

Kiyonari

Saito

et al. 2009

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

Self Cite

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“…This "either/or" scenario of DNA ligase substrate specificity has been roiled by several seemingly conflicting reports concerning the nucleotide specificity of archaeal DNA ligases. All archaeal proteomes include an ATP-dependent DNA ligase that resembles in all structural respects (amino acid sequence; conservation of NTase motifs, including motif VI; and tertiary structure composed of the N-terminal DBD and the central NTase and C-terminal OB domains) (20,21) the canonical ATP-dependent DNA ligases of eukaryal cells. Biochemical characterization of several archaeal DNA ligases verified their strict dependence on ATP and failure to utilize NAD ϩ (summarized in Ref.…”

Section: Is There An "Undifferentiated" Ligase With Respect To the Sumentioning

confidence: 99%

DNA Ligases: Progress and Prospects

Shuman

2009

Journal of Biological Chemistry

167

180

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DNA ligases seal 5-PO 4 and 3-OH polynucleotide ends via three nucleotidyl transfer steps involving ligase-adenylate and DNA-adenylate intermediates. DNA ligases are essential guardians of genomic integrity, and ligase dysfunction underlies human genetic disease syndromes. Crystal structures of DNA ligases bound to nucleotide and nucleic acid substrates have illuminated how ligase reaction chemistry is catalyzed, how ligases recognize damaged DNA ends, and how protein domain movements and active-site remodeling are used to choreograph the end-joining pathway. Although a shared feature of DNA ligases is their envelopment of the nicked duplex as a C-shaped protein clamp, they accomplish this feat by using remarkably different accessory structural modules and domain topologies. As structural, biochemical, and phylogenetic insights coalesce, we can expect advances on several fronts, including (i) pharmacological targeting of ligases for antibacterial and anticancer therapies and (ii) the discovery and design of new strand-sealing enzymes with unique substrate specificities. DNA LigaseThe discovery of DNA ligases in 1967 by the Gellert, Lehman, Richardson, and Hurwitz laboratories was a watershed event in molecular biology (reviewed in Ref. 1). By joining 3Ј-OH and 5Ј-PO 4 termini to form a phosphodiester, DNA ligases are the sine qua non of genome integrity. They are essential for DNA replication and repair in all organisms. Ligases were critical reagents in the development of molecular cloning and many subsequent ramifications of DNA biotechnology, including molecular diagnostics and SOLiD sequencing methods. Ligases are elegant and versatile enzymes and are enjoying a research renaissance in light of discoveries that most organisms have multiple ligases that either function in DNA replication (by joining Okazaki fragments) or are dedicated to particular DNA repair pathways, such as nucleotide excision repair, base excision repair, single-strand break repair, or the repair of doublestrand breaks via nonhomologous end joining (2-4). Genetic deficiencies in human DNA ligases have been associated with clinical syndromes marked by immunodeficiency, radiation sensitivity, and developmental abnormalities (3). The physiology and division of labor among cellular DNA ligases are the subjects of recent reviews (2-4) and will not be covered here. This minireview will focus on new insights to ligase mechanism and evolution from ligase structure.DNA ligation entails three sequential nucleotidyl transfer steps (Fig. 1). In the first step, nucleophilic attack on the ␣-phosphorus of ATP or NAD ϩ by ligase results in release of PP i or NMN and formation of a covalent ligase-adenylate intermediate in which AMP is linked via a P-N bond to N-of a lysine. In the second step, the AMP is transferred to the 5Ј-end of the 5Ј-phosphate-terminated DNA strand to form DNAadenylate. In this reaction, the 5Ј-phosphate oxygen of the DNA strand attacks the phosphorus of ligase-adenylate, and the active-site lysine is the leaving group. In the thir...

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“…The structure of human DNA ligase I has been solved (Pascal et al 2004 ) . In addition, archaea also possess ATP-dependent DNA ligases and the structures of several of these (as well as the structure of several ATP-dependent DNA ligases from eukaryotic viruses and bacteriophage) have been determined (Kim et al 2009 ;Nishida et al 2006 ;Pascal et al 2006 ) , providing insights into the conserved ligase catalytic mechanism (see Chap. 17 for details).…”

Section: Okazaki Fragment Processingmentioning

confidence: 99%

Composition and Dynamics of the Eukaryotic Replisome: A Brief Overview

MacNeill

2012

Subcellular Biochemistry

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High-fidelity chromosomal DNA replication is vital for maintaining the integrity of the genetic material in all forms of cellular life. In eukaryotic cells, around 40-50 distinct conserved polypeptides are essential for chromosome replication, the majority of which are themselves component parts of a series of elaborate molecular machines that comprise the replication apparatus or replisome. How these complexes are assembled, what structures they adopt, how they perform their functions, and how those functions are regulated, are key questions for understanding how genome duplication occurs. Here I present a brief overview of current knowledge of the composition of the replisome and the dynamic molecular events that underlie chromosomal DNA replication in eukaryotic cells.

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The Closed Structure of an Archaeal DNA Ligase from Pyrococcus furiosus

Cited by 59 publications

References 30 publications

Mechanism of replication machinery assembly as revealed by the DNA ligase–PCNA–DNA complex architecture

Mechanism of replication machinery assembly as revealed by the DNA ligase–PCNA–DNA complex architecture

DNA Ligases: Progress and Prospects

Composition and Dynamics of the Eukaryotic Replisome: A Brief Overview

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