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PDBsum entry 2p6u
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DNA binding protein PDB id
2p6u

 

 

 

 

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Contents
Protein chain
671 a.a. *
Ligands
PO4 ×10
* Residue conservation analysis
PDB id:
2p6u
Name: DNA binding protein
Title: Apo structure of the hel308 superfamily 2 helicase
Structure: Afuhel308 helicase. Chain: a. Engineered: yes
Source: Archaeoglobus fulgidus. Organism_taxid: 2234. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
3.14Å     R-factor:   0.230     R-free:   0.276
Authors: K.Buettner,S.Nehring,K.P.Hopfner
Key ref:
K.Büttner et al. (2007). Structural basis for DNA duplex separation by a superfamily-2 helicase. Nat Struct Biol, 14, 647-652. PubMed id: 17558417 DOI: 10.1038/nsmb1246
Date:
19-Mar-07     Release date:   12-Jun-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
No UniProt id for this chain
Struc:  
Struc: 671 a.a.
Key:    Secondary structure  CATH domain

 

 
DOI no: 10.1038/nsmb1246 Nat Struct Biol 14:647-652 (2007)
PubMed id: 17558417  
 
 
Structural basis for DNA duplex separation by a superfamily-2 helicase.
K.Büttner, S.Nehring, K.P.Hopfner.
 
  ABSTRACT  
 
To reveal the mechanism of processive strand separation by superfamily-2 (SF2) 3'-->5' helicases, we determined apo and DNA-bound crystal structures of archaeal Hel308, a helicase that unwinds lagging strands and is related to human DNA polymerase theta. Our structure captures the duplex-unwinding reaction, shows that initial strand separation does not require ATP and identifies a prominent beta-hairpin loop as the unwinding element. Similar loops in hepatitis C virus NS3 helicase and RNA-decay factors support the idea that this duplex-unwinding mechanism is applicable to a broad subset of SF2 helicases. Comparison with ATP-bound SF2 enzymes suggests that ATP promotes processive unwinding of 1 base pair by ratchet-like transport of the 3' product strand. Our results provide a first structural framework for strand separation by processive SF2 3'-->5' helicases and reveal important mechanistic differences from SF1 helicases.
 
  Selected figure(s)  
 
Figure 1.
(a) Schematic of the five domains of Hel308. Domain boundaries are indicated on top, sequence motifs beneath. Roman numerals, SF2 helicase motifs; , -hairpin loop; R, ratchet helix; RAR, Arg-Ala-Arg motif. (b) Hel308 (ribbon, colored as in a) in complex with the 15-base-pair DNA duplex and 10-base single-stranded 3' tail (beige sticks). (c) Schematic showing key interactions (dashed lines) of Hel308 with the partially unwound DNA substrate. 		Figure 4.
Shown are products of proteolysis digestion of archaeal Hel308 by indicated amounts of proteinase K in the presence or absence of AMP-PNP and DNA.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2007, 14, 647-652) copyright 2007.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21059676 B.Lucic, Y.Zhang, O.King, R.Mendoza-Maldonado, M.Berti, F.H.Niesen, N.A.Burgess-Brown, A.C.Pike, C.D.Cooper, O.Gileadi, and A.Vindigni (2011).
A prominent beta-hairpin structure in the winged-helix domain of RECQ1 is required for DNA unwinding and oligomer formation.
  Nucleic Acids Res, 39, 1703-1717.  
21441902 B.Montpetit, N.D.Thomsen, K.J.Helmke, M.A.Seeliger, J.M.Berger, and K.Weis (2011).
A conserved mechanism of DEAD-box ATPase activation by nucleoporins and InsP6 in mRNA export.
  Nature, 472, 238-242.
PDB codes: 3peu 3pev 3pew 3pex 3pey 3pez 3rrm 3rrn
20813532 E.Jankowsky (2011).
RNA helicases at work: binding and rearranging.
  Trends Biochem Sci, 36, 19-29.  
21265761 I.L.Woodman, and E.L.Bolt (2011).
Winged helix domains with unknown function in Hel308 and related helicases.
  Biochem Soc Trans, 39, 140-144.  
20233727 B.Y.Pan, S.X.Dou, Y.Yang, Y.N.Xu, E.Bugnard, X.Y.Ding, L.Zhang, P.Y.Wang, M.Li, and X.G.Xi (2010).
Mutual inhibition of RecQ molecules in DNA unwinding.
  J Biol Chem, 285, 15884-15893.  
20832723 G.Hauk, J.N.McKnight, I.M.Nodelman, and G.D.Bowman (2010).
The chromodomains of the Chd1 chromatin remodeler regulate DNA access to the ATPase motor.
  Mol Cell, 39, 711-723.
PDB code: 3mwy
20512115 H.Walbott, S.Mouffok, R.Capeyrou, S.Lebaron, O.Humbert, H.van Tilbeurgh, Y.Henry, and N.Leulliot (2010).
Prp43p contains a processive helicase structural architecture with a specific regulatory domain.
  EMBO J, 29, 2194-2204.
PDB code: 2xau
21058657 J.Bernstein, J.D.Ballin, D.N.Patterson, G.M.Wilson, and E.A.Toth (2010).
Unique properties of the Mtr4p-poly(A) complex suggest a role in substrate targeting.
  Biochemistry, 49, 10357-10370.  
20566885 J.R.Weir, F.Bonneau, J.Hentschel, and E.Conti (2010).
Structural analysis reveals the characteristic features of Mtr4, a DExH helicase involved in nuclear RNA processing and surveillance.
  Proc Natl Acad Sci U S A, 107, 12139-12144.
PDB code: 2xgj
19933257 J.Rudolf, C.Rouillon, U.Schwarz-Linek, and M.F.White (2010).
The helicase XPD unwinds bubble structures and is not stalled by DNA lesions removed by the nucleotide excision repair pathway.
  Nucleic Acids Res, 38, 931-941.  
20159463 K.Kitano, S.Y.Kim, and T.Hakoshima (2010).
Structural basis for DNA strand separation by the unconventional winged-helix domain of RecQ helicase WRN.
  Structure, 18, 177-187.
PDB code: 3aaf
20211839 M.Gyimesi, K.Sarlós, and M.Kovács (2010).
Processive translocation mechanism of the human Bloom's syndrome helicase along single-stranded DNA.
  Nucleic Acids Res, 38, 4404-4414.  
20512111 R.N.Jackson, A.A.Klauer, B.J.Hintze, H.Robinson, A.van Hoof, and S.J.Johnson (2010).
The crystal structure of Mtr4 reveals a novel arch domain required for rRNA processing.
  EMBO J, 29, 2205-2216.
PDB code: 3l9o
20482310 S.C.Wolski, J.Kuper, and C.Kisker (2010).
The XPD helicase: XPanDing archaeal XPD structures to get a grip on human DNA repair.
  Biol Chem, 391, 761-765.  
20110368 S.D.Taylor, A.Solem, J.Kawaoka, and A.M.Pyle (2010).
The NPH-II helicase displays efficient DNA x RNA helicase activity and a pronounced purine sequence bias.
  J Biol Chem, 285, 11692-11703.  
20192763 W.Yang (2010).
Lessons learned from UvrD helicase: mechanism for directional movement.
  Annu Rev Biophys, 39, 367-385.  
20168331 Y.He, G.R.Andersen, and K.H.Nielsen (2010).
Structural basis for the function of DEAH helicases.
  EMBO Rep, 11, 180-186.
PDB code: 3kx2
19151156 A.C.Pike, B.Shrestha, V.Popuri, N.Burgess-Brown, L.Muzzolini, S.Costantini, A.Vindigni, and O.Gileadi (2009).
Structure of the human RECQ1 helicase reveals a putative strand-separation pin.
  Proc Natl Acad Sci U S A, 106, 1039-1044.
PDB code: 2v1x
19949442 A.Vindigni, and I.D.Hickson (2009).
RecQ helicases: multiple structures for multiple functions?
  HFSP J, 3, 153-164.  
  20161209 C.A.Belon, and D.N.Frick (2009).
Helicase inhibitors as specifically targeted antiviral therapy for hepatitis C.
  Future Virol, 4, 277-293.  
19878916 C.Zhao, D.L.Bellur, S.Lu, F.Zhao, M.A.Grassi, S.J.Bowne, L.S.Sullivan, S.P.Daiger, L.J.Chen, C.P.Pang, K.Zhao, J.P.Staley, and C.Larsson (2009).
Autosomal-dominant retinitis pigmentosa caused by a mutation in SNRNP200, a gene required for unwinding of U4/U6 snRNAs.
  Am J Hum Genet, 85, 617-627.  
19525970 L.Zhang, T.Xu, C.Maeder, L.O.Bud, J.Shanks, J.Nix, C.Guthrie, J.A.Pleiss, and R.Zhao (2009).
Structural evidence for consecutive Hel308-like modules in the spliceosomal ATPase Brr2.
  Nat Struct Mol Biol, 16, 731-739.
PDB code: 3hib
19700770 M.N.Murphy, P.Gong, K.Ralto, L.Manelyte, N.J.Savery, and K.Theis (2009).
An N-terminal clamp restrains the motor domains of the bacterial transcription-repair coupling factor Mfd.
  Nucleic Acids Res, 37, 6042-6053.
PDB code: 3hjh
19324887 M.Nongkhlaw, P.Dutta, J.W.Hockensmith, S.S.Komath, and R.Muthuswami (2009).
Elucidating the mechanism of DNA-dependent ATP hydrolysis mediated by DNA-dependent ATPase A, a member of the SWI2/SNF2 protein family.
  Nucleic Acids Res, 37, 3332-3341.  
19159486 T.Oyama, H.Oka, K.Mayanagi, T.Shirai, K.Matoba, R.Fujikane, Y.Ishino, and K.Morikawa (2009).
Atomic structures and functional implications of the archaeal RecQ-like helicase Hjm.
  BMC Struct Biol, 9, 2.
PDB codes: 2zj2 2zj5 2zj8 2zja
19716790 V.Pena, S.M.Jovin, P.Fabrizio, J.Orlowski, J.M.Bujnicki, R.Lührmann, and M.C.Wahl (2009).
Common design principles in the spliceosomal RNA helicase Brr2 and in the Hel308 DNA helicase.
  Mol Cell, 35, 454-466.
PDB codes: 3im1 3im2
19452133 W.Hwang, and M.J.Lang (2009).
Mechanical design of translocating motor proteins.
  Cell Biochem Biophys, 54, 11-22.  
19099189 Y.Wu, A.N.Suhasini, and R.M.Brosh (2009).
Welcome the family of FANCJ-like helicases to the block of genome stability maintenance proteins.
  Cell Mol Life Sci, 66, 1209-1222.  
18643303 A.Garai, D.Chowdhury, and M.D.Betterton (2008).
Two-state model for helicase translocation and unwinding of nucleic acids.
  Phys Rev E Stat Nonlin Soft Matter Phys, 77, 061910.  
18573084 A.M.Pyle (2008).
Translocation and unwinding mechanisms of RNA and DNA helicases.
  Annu Rev Biophys, 37, 317-336.  
19008861 D.Luo, T.Xu, R.P.Watson, D.Scherer-Becker, A.Sampath, W.Jahnke, S.S.Yeong, C.H.Wang, S.P.Lim, A.Strongin, S.G.Vasudevan, and J.Lescar (2008).
Insights into RNA unwinding and ATP hydrolysis by the flavivirus NS3 protein.
  EMBO J, 27, 3209-3219.
PDB codes: 2jlq 2jlr 2jls 2jlu 2jlv 2jlw 2jlx 2jly 2jlz
18329872 E.J.Enemark, and L.Joshua-Tor (2008).
On helicases and other motor proteins.
  Curr Opin Struct Biol, 18, 243-257.  
18510925 H.Liu, J.Rudolf, K.A.Johnson, S.A.McMahon, M.Oke, L.Carter, A.M.McRobbie, S.E.Brown, J.H.Naismith, and M.F.White (2008).
Structure of the DNA repair helicase XPD.
  Cell, 133, 801-812.
PDB code: 2vl7
18332124 J.Banroques, O.Cordin, M.Doère, P.Linder, and N.K.Tanner (2008).
A conserved phenylalanine of motif IV in superfamily 2 helicases is required for cooperative, ATP-dependent binding of RNA substrates in DEAD-box proteins.
  Mol Cell Biol, 28, 3359-3371.  
18096702 J.Bernstein, D.N.Patterson, G.M.Wilson, and E.A.Toth (2008).
Characterization of the essential activities of Saccharomyces cerevisiae Mtr4p, a 3'->5' helicase partner of the nuclear exosome.
  J Biol Chem, 283, 4930-4942.  
18056710 J.D.Richards, K.A.Johnson, H.Liu, A.M.McRobbie, S.McMahon, M.Oke, L.Carter, J.H.Naismith, and M.F.White (2008).
Structure of the DNA repair helicase hel308 reveals DNA binding and autoinhibitory domains.
  J Biol Chem, 283, 5118-5126.
PDB code: 2va8
18668125 K.Saikrishnan, S.P.Griffiths, N.Cook, R.Court, and D.B.Wigley (2008).
DNA binding to RecD: role of the 1B domain in SF1B helicase activity.
  EMBO J, 27, 2222-2229.
PDB codes: 3e1s 3k70
18510924 L.Fan, J.O.Fuss, Q.J.Cheng, A.S.Arvai, M.Hammel, V.A.Roberts, P.K.Cooper, and J.A.Tainer (2008).
XPD helicase structures and activities: insights into the cancer and aging phenotypes from XPD mutations.
  Cell, 133, 789-800.
PDB codes: 3crv 3crw
18647240 N.D.Thomsen, and J.M.Berger (2008).
Structural frameworks for considering microbial protein- and nucleic acid-dependent motor ATPases.
  Mol Microbiol, 69, 1071-1090.  
18029358 R.A.Pugh, M.Honda, H.Leesley, A.Thomas, Y.Lin, M.J.Nilges, I.K.Cann, and M.Spies (2008).
The iron-containing domain is essential in Rad3 helicases for coupling of ATP hydrolysis to DNA translocation and for targeting the helicase to the single-stranded DNA-double-stranded DNA junction.
  J Biol Chem, 283, 1732-1743.  
18267970 R.Lewis, H.Dürr, K.P.Hopfner, and J.Michaelis (2008).
Conformational changes of a Swi2/Snf2 ATPase during its mechano-chemical cycle.
  Nucleic Acids Res, 36, 1881-1890.  
18388857 R.Seidel, J.G.Bloom, C.Dekker, and M.D.Szczelkun (2008).
Motor step size and ATP coupling efficiency of the dsDNA translocase EcoR124I.
  EMBO J, 27, 1388-1398.  
18578568 S.C.Wolski, J.Kuper, P.Hänzelmann, J.J.Truglio, D.L.Croteau, B.Van Houten, and C.Kisker (2008).
Crystal structure of the FeS cluster-containing nucleotide excision repair helicase XPD.
  PLoS Biol, 6, e149.
PDB code: 2vsf
18321528 S.J.Johnson, D.Close, H.Robinson, I.Vallet-Gely, S.L.Dove, and C.P.Hill (2008).
Crystal structure and RNA binding of the Tex protein from Pseudomonas aeruginosa.
  J Mol Biol, 377, 1460-1473.
PDB codes: 3bzc 3bzk
18414490 T.M.Lohman, E.J.Tomko, and C.G.Wu (2008).
Non-hexameric DNA helicases and translocases: mechanisms and regulation.
  Nat Rev Mol Cell Biol, 9, 391-401.  
18448429 V.Popuri, C.Z.Bachrati, L.Muzzolini, G.Mosedale, S.Costantini, E.Giacomini, I.D.Hickson, and A.Vindigni (2008).
The Human RecQ helicases, BLM and RECQ1, display distinct DNA substrate specificities.
  J Biol Chem, 283, 17766-17776.  
18296528 Z.Li, S.Lu, G.Hou, X.Ma, D.Sheng, J.Ni, and Y.Shen (2008).
Hjm/Hel308A DNA helicase from Sulfolobus tokodaii promotes replication fork regression and interacts with Hjc endonuclease in vitro.
  J Bacteriol, 190, 3006-3017.  
17921146 R.K.Beran, V.Serebrov, and A.M.Pyle (2007).
The serine protease domain of hepatitis C viral NS3 activates RNA helicase activity by promoting the binding of RNA substrate.
  J Biol Chem, 282, 34913-34920.  
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.

 

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