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PDBsum entry 2hik

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protein Protein-protein interface(s) links
Replication PDB id
2hik
Jmol
Contents
Protein chains
249 a.a. *
244 a.a. *
243 a.a. *
* Residue conservation analysis
PDB id:
2hik
Name: Replication
Title: Heterotrimeric pcna sliding clamp
Structure: Pcna1 (sso0397). Chain: a, l, x. Synonym: DNA polymerase sliding clamp b, proliferating cell antigen homolog b, pcna b. Engineered: yes. Pcna2 (sso1047). Chain: b, m, y. Synonym: DNA polymerase sliding clamp c, proliferating cell antigen homolog c, pcna c.
Source: Sulfolobus solfataricus. Organism_taxid: 2287. Gene: pcnb, pcna-2. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: pcnc, pcna-2. Gene: pcna, pcna-1. Expression_system_taxid: 562
Biol. unit: Trimer (from PQS)
Resolution:
3.30Å     R-factor:   0.239     R-free:   0.299
Authors: J.M.Pascal,O.V.Tsodikov,T.Ellenberger
Key ref:
J.M.Pascal et al. (2006). A flexible interface between DNA ligase and PCNA supports conformational switching and efficient ligation of DNA. Mol Cell, 24, 279-291. PubMed id: 17052461 DOI: 10.1016/j.molcel.2006.08.015
Date:
29-Jun-06     Release date:   07-Nov-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P57766  (PCNA2_SULSO) -  DNA polymerase sliding clamp 1
Seq:
Struc:
249 a.a.
249 a.a.
Protein chains
Pfam   ArchSchema ?
Q97Z84  (PCNA3_SULSO) -  DNA polymerase sliding clamp 2
Seq:
Struc:
245 a.a.
244 a.a.
Protein chains
Pfam   ArchSchema ?
P57765  (PCNA1_SULSO) -  DNA polymerase sliding clamp 3
Seq:
Struc:
244 a.a.
243 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     PCNA complex   1 term 
  Biological process     regulation of DNA replication   2 terms 
  Biochemical function     DNA polymerase processivity factor activity     2 terms  

 

 
DOI no: 10.1016/j.molcel.2006.08.015 Mol Cell 24:279-291 (2006)
PubMed id: 17052461  
 
 
A flexible interface between DNA ligase and PCNA supports conformational switching and efficient ligation of DNA.
J.M.Pascal, O.V.Tsodikov, G.L.Hura, W.Song, E.A.Cotner, S.Classen, A.E.Tomkinson, J.A.Tainer, T.Ellenberger.
 
  ABSTRACT  
 
DNA sliding clamps encircle DNA and provide binding sites for many DNA-processing enzymes. However, it is largely unknown how sliding clamps like proliferating cell nuclear antigen (PCNA) coordinate multistep DNA transactions. We have determined structures of Sulfolobus solfataricus DNA ligase and heterotrimeric PCNA separately by X-ray diffraction and in complex by small-angle X-ray scattering (SAXS). Three distinct PCNA subunits assemble into a protein ring resembling the homotrimeric PCNA of humans but with three unique protein-binding sites. In the absence of nicked DNA, the Sulfolobus solfataricus DNA ligase has an open, extended conformation. When complexed with heterotrimeric PCNA, the DNA ligase binds to the PCNA3 subunit and ligase retains an open, extended conformation. A closed, ring-shaped conformation of ligase catalyzes a DNA end-joining reaction that is strongly stimulated by PCNA. This open-to-closed switch in the conformation of DNA ligase is accommodated by a malleable interface with PCNA that serves as an efficient platform for DNA ligation.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Conformational States of DNA Ligase
Figure 3.
Figure 3. ssLig Structure and Conformation in Solution
 
  The above figures are reprinted by permission from Cell Press: Mol Cell (2006, 24, 279-291) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
23396808 S.Classen, G.L.Hura, J.M.Holton, R.P.Rambo, I.Rodic, P.J.McGuire, K.Dyer, M.Hammel, G.Meigs, K.A.Frankel, and J.A.Tainer (2013).
Implementation and performance of SIBYLS: a dual endstation small-angle X-ray scattering and macromolecular crystallography beamline at the Advanced Light Source.
  J Appl Crystallogr, 46, 1.  
21364740 A.De Biasio, R.Sánchez, J.Prieto, M.Villate, R.Campos-Olivas, and F.J.Blanco (2011).
Reduced Stability and Increased Dynamics in the Human Proliferating Cell Nuclear Antigen (PCNA) Relative to the Yeast Homolog.
  PLoS One, 6, e16600.  
21265749 T.R.Beattie, and S.D.Bell (2011).
The role of the DNA sliding clamp in Okazaki fragment maturation in archaea and eukaryotes.
  Biochem Soc Trans, 39, 70-76.  
19913033 A.Piserchio, P.A.Nair, S.Shuman, and R.Ghose (2010).
Solution NMR studies of Chlorella virus DNA ligase-adenylate.
  J Mol Biol, 395, 291-308.  
20120026 D.A.Jacques, and J.Trewhella (2010).
Small-angle scattering for structural biology--expanding the frontier while avoiding the pitfalls.
  Protein Sci, 19, 642-657.  
20008103 R.D.Hutton, T.D.Craggs, M.F.White, and J.C.Penedo (2010).
PCNA and XPF cooperate to distort DNA substrates.
  Nucleic Acids Res, 38, 1664-1675.  
  20862368 T.Ochi, B.L.Sibanda, Q.Wu, D.Y.Chirgadze, V.M.Bolanos-Garcia, and T.L.Blundell (2010).
Structural biology of DNA repair: spatial organisation of the multicomponent complexes of nonhomologous end joining.
  J Nucleic Acids, 2010, 0.  
19576301 Z.Zhuang, and Y.Ai (2010).
Processivity factor of DNA polymerase and its expanding role in normal and translesion DNA synthesis.
  Biochim Biophys Acta, 1804, 1081-1093.  
19628465 A.López Castel, A.E.Tomkinson, and C.E.Pearson (2009).
CTG/CAG repeat instability is modulated by the levels of human DNA ligase I and its interaction with proliferating cell nuclear antigen: a distinction between replication and slipped-DNA repair.
  J Biol Chem, 284, 26631-26645.  
  19342782 E.Y.Bezsudnova, M.V.Kovalchuk, A.V.Mardanov, K.M.Poliakov, V.O.Popov, N.V.Ravin, K.G.Skryabin, V.A.Smagin, T.N.Stekhanova, and T.V.Tikhonova (2009).
Overexpression, purification and crystallization of a thermostable DNA ligase from the archaeon Thermococcus sp. 1519.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 65, 368-371.  
19881914 F.J.López de Saro (2009).
Regulation of interactions with sliding clamps during DNA replication and repair.
  Curr Genomics, 10, 206-215.  
19620974 G.L.Hura, A.L.Menon, M.Hammel, R.P.Rambo, F.L.Poole, S.E.Tsutakawa, F.E.Jenney, S.Classen, K.A.Frankel, R.C.Hopkins, S.J.Yang, J.W.Scott, B.D.Dillard, M.W.Adams, and J.A.Tainer (2009).
Robust, high-throughput solution structural analyses by small angle X-ray scattering (SAXS).
  Nat Methods, 6, 606-612.  
19596905 K.K.Karanja, and D.M.Livingston (2009).
C-terminal flap endonuclease (rad27) mutations: lethal interactions with a DNA ligase I mutation (cdc9-p) and suppression by proliferating cell nuclear antigen (POL30) in Saccharomyces cerevisiae.
  Genetics, 183, 63-78.  
19255439 K.Mayanagi, S.Kiyonari, M.Saito, T.Shirai, Y.Ishino, and K.Morikawa (2009).
Mechanism of replication machinery assembly as revealed by the DNA ligase-PCNA-DNA complex architecture.
  Proc Natl Acad Sci U S A, 106, 4647-4652.  
19804755 R.S.Williams, G.E.Dodson, O.Limbo, Y.Yamada, J.S.Williams, G.Guenther, S.Classen, J.N.Glover, H.Iwasaki, P.Russell, and J.A.Tainer (2009).
Nbs1 flexibly tethers Ctp1 and Mre11-Rad50 to coordinate DNA double-strand break processing and repair.
  Cell, 139, 87-99.
PDB codes: 3hue 3huf
19329793 S.Shuman (2009).
DNA ligases: progress and prospects.
  J Biol Chem, 284, 17365-17369.  
19523882 W.Song, J.M.Pascal, T.Ellenberger, and A.E.Tomkinson (2009).
The DNA binding domain of human DNA ligase I interacts with both nicked DNA and the DNA sliding clamps, PCNA and hRad9-hRad1-hHus1.
  DNA Repair (Amst), 8, 912-919.  
18238776 E.Cotner-Gohara, I.K.Kim, A.E.Tomkinson, and T.Ellenberger (2008).
Two DNA-binding and nick recognition modules in human DNA ligase III.
  J Biol Chem, 283, 10764-10772.  
18312273 I.Dionne, N.J.Brown, R.Woodgate, and S.D.Bell (2008).
On the mechanism of loading the PCNA sliding clamp by RFC.
  Mol Microbiol, 68, 216-222.  
18262407 J.M.Pascal (2008).
DNA and RNA ligases: structural variations and shared mechanisms.
  Curr Opin Struct Biol, 18, 96.  
18658243 M.Honda, T.Fujisawa, T.Shibata, and T.Mikawa (2008).
RecR forms a ring-like tetramer that encircles dsDNA by forming a complex with RecF.
  Nucleic Acids Res, 36, 5013-5020.  
18842000 R.A.Edwards, M.S.Lee, S.E.Tsutakawa, R.S.Williams, J.A.Tainer, and J.N.Glover (2008).
The BARD1 C-terminal domain structure and interactions with polyadenylation factor CstF-50.
  Biochemistry, 47, 11446-11456.  
18948279 R.D.Hutton, J.A.Roberts, J.C.Penedo, and M.F.White (2008).
PCNA stimulates catalysis by structure-specific nucleases using two distinct mechanisms: substrate targeting and catalytic step.
  Nucleic Acids Res, 36, 6720-6727.  
18326858 R.R.Iyer, T.J.Pohlhaus, S.Chen, G.L.Hura, L.Dzantiev, L.S.Beese, and P.Modrich (2008).
The MutSalpha-proliferating cell nuclear antigen interaction in human DNA mismatch repair.
  J Biol Chem, 283, 13310-13319.  
18518823 T.Ellenberger, and A.E.Tomkinson (2008).
Eukaryotic DNA ligases: structural and functional insights.
  Annu Rev Biochem, 77, 313-338.  
18703842 V.Hlinkova, G.Xing, J.Bauer, Y.J.Shin, I.Dionne, K.R.Rajashankar, S.D.Bell, and H.Ling (2008).
Structures of monomeric, dimeric and trimeric PCNA: PCNA-ring assembly and opening.
  Acta Crystallogr D Biol Crystallogr, 64, 941-949.
PDB codes: 2ijx 2io4 2nti
18078545 C.D.Putnam, M.Hammel, G.L.Hura, and J.A.Tainer (2007).
X-ray solution scattering (SAXS) combined with crystallography and computation: defining accurate macromolecular structures, conformations and assemblies in solution.
  Q Rev Biophys, 40, 191-285.  
17512402 G.L.Moldovan, B.Pfander, and S.Jentsch (2007).
PCNA, the maestro of the replication fork.
  Cell, 129, 665-679.  
17466627 J.Nandakumar, P.A.Nair, and S.Shuman (2007).
Last stop on the road to repair: structure of E. coli DNA ligase bound to nicked DNA-adenylate.
  Mol Cell, 26, 257-271.
PDB code: 2owo
17493121 K.Imamura, K.Fukunaga, Y.Kawarabayasi, and Y.Ishino (2007).
Specific interactions of three proliferating cell nuclear antigens with replication-related proteins in Aeropyrum pernix.
  Mol Microbiol, 64, 308-318.  
17576694 L.Schermelleh, A.Haemmer, F.Spada, N.Rösing, D.Meilinger, U.Rothbauer, M.C.Cardoso, and H.Leonhardt (2007).
Dynamics of Dnmt1 interaction with the replication machinery and its role in postreplicative maintenance of DNA methylation.
  Nucleic Acids Res, 35, 4301-4312.  
17618295 P.A.Nair, J.Nandakumar, P.Smith, M.Odell, C.D.Lima, and S.Shuman (2007).
Structural basis for nick recognition by a minimal pluripotent DNA ligase.
  Nat Struct Mol Biol, 14, 770-778.
PDB codes: 2q2t 2q2u
17713585 R.S.Williams, J.S.Williams, and J.A.Tainer (2007).
Mre11-Rad50-Nbs1 is a keystone complex connecting DNA repair machinery, double-strand break signaling, and the chromatin template.
  Biochem Cell Biol, 85, 509-520.  
17487442 S.Kiyonari, T.Kamigochi, and Y.Ishino (2007).
A single amino acid substitution in the DNA-binding domain of Aeropyrum pernix DNA ligase impairs its interaction with proliferating cell nuclear antigen.
  Extremophiles, 11, 675-684.  
17531814 S.S.Shell, C.D.Putnam, and R.D.Kolodner (2007).
The N terminus of Saccharomyces cerevisiae Msh6 is an unstructured tether to PCNA.
  Mol Cell, 26, 565-578.  
17308348 S.Vijayakumar, B.R.Chapados, K.H.Schmidt, R.D.Kolodner, J.A.Tainer, and A.E.Tomkinson (2007).
The C-terminal domain of yeast PCNA is required for physical and functional interactions with Cdc9 DNA ligase.
  Nucleic Acids Res, 35, 1624-1637.
PDB code: 2od8
17561505 W.Song, D.S.Levin, J.Varkey, S.Post, V.P.Bermudez, J.Hurwitz, and A.E.Tomkinson (2007).
A conserved physical and functional interaction between the cell cycle checkpoint clamp loader and DNA ligase I of eukaryotes.
  J Biol Chem, 282, 22721-22730.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.