SF1 and SF2 Helicases: Family Matters

Overview

Journal Curr Opin Struct Biol

Date 2010 May 12

PMID 20456941

Citations 510

Authors

Margaret E Fairman-Williams

Ulf-Peter Guenther

Eckhard Jankowsky

Affiliations

Soon will be listed here.

Abstract

Helicases of the superfamily (SF) 1 and 2 are involved in virtually all aspects of RNA and DNA metabolism. SF1 and SF2 helicases share a catalytic core with high structural similarity, but different enzymes even within each SF perform a wide spectrum of distinct functions on diverse substrates. To rationalize similarities and differences between these helicases, we outline a classification based on protein families that are characterized by typical sequence, structural, and mechanistic features. This classification complements and extends existing SF1 and SF2 helicase categorizations and highlights major structural and functional themes for these proteins. We discuss recent data in the context of this unifying view of SF1 and SF2 helicases.

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References

Tijerina P, Bhaskaran H, Russell R . Nonspecific binding to structured RNA and preferential unwinding of an exposed helix by the CYT-19 protein, a DEAD-box RNA chaperone. Proc Natl Acad Sci U S A. 2006; 103(45):16698-703. PMC: 1636518. DOI: 10.1073/pnas.0603127103. View

Capp C, Wu J, Hsieh T . Drosophila RecQ4 has a 3'-5' DNA helicase activity that is essential for viability. J Biol Chem. 2009; 284(45):30845-52. PMC: 2781483. DOI: 10.1074/jbc.M109.008052. View

Zhang L, Xu T, Maeder C, Bud L, Shanks J, Nix J . Structural evidence for consecutive Hel308-like modules in the spliceosomal ATPase Brr2. Nat Struct Mol Biol. 2009; 16(7):731-9. PMC: 2743687. DOI: 10.1038/nsmb.1625. View

Lohman T, Tomko E, Wu C . Non-hexameric DNA helicases and translocases: mechanisms and regulation. Nat Rev Mol Cell Biol. 2008; 9(5):391-401. DOI: 10.1038/nrm2394. View

Banroques J, Doere M, Dreyfus M, Linder P, Tanner N . Motif III in superfamily 2 "helicases" helps convert the binding energy of ATP into a high-affinity RNA binding site in the yeast DEAD-box protein Ded1. J Mol Biol. 2009; 396(4):949-66. DOI: 10.1016/j.jmb.2009.12.025. View

Bizebard T, Ferlenghi I, Iost I, Dreyfus M . Studies on three E. coli DEAD-box helicases point to an unwinding mechanism different from that of model DNA helicases. Biochemistry. 2004; 43(24):7857-66. DOI: 10.1021/bi049852s. View

Soultanas P, Dillingham M, Wiley P, Webb M, Wigley D . Uncoupling DNA translocation and helicase activity in PcrA: direct evidence for an active mechanism. EMBO J. 2000; 19(14):3799-810. PMC: 313991. DOI: 10.1093/emboj/19.14.3799. View

Klostermeier D, Rudolph M . A novel dimerization motif in the C-terminal domain of the Thermus thermophilus DEAD box helicase Hera confers substantial flexibility. Nucleic Acids Res. 2008; 37(2):421-30. PMC: 2632915. DOI: 10.1093/nar/gkn947. View

Bernstein E, Caudy A, Hammond S, Hannon G . Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature. 2001; 409(6818):363-6. DOI: 10.1038/35053110. View

10.

Wolski S, Kuper J, Hanzelmann P, Truglio J, Croteau D, Van Houten B . Crystal structure of the FeS cluster-containing nucleotide excision repair helicase XPD. PLoS Biol. 2008; 6(6):e149. PMC: 2435149. DOI: 10.1371/journal.pbio.0060149. View

11.

Sanjuan R, Marin I . Tracing the origin of the compensasome: evolutionary history of DEAH helicase and MYST acetyltransferase gene families. Mol Biol Evol. 2001; 18(3):330-43. DOI: 10.1093/oxfordjournals.molbev.a003809. View

12.

Killoran M, Keck J . Structure and function of the regulatory C-terminal HRDC domain from Deinococcus radiodurans RecQ. Nucleic Acids Res. 2008; 36(9):3139-49. PMC: 2396406. DOI: 10.1093/nar/gkn143. View

13.

Yang Q, Del Campo M, Lambowitz A, Jankowsky E . DEAD-box proteins unwind duplexes by local strand separation. Mol Cell. 2007; 28(2):253-63. DOI: 10.1016/j.molcel.2007.08.016. View

14.

Frick D, Lam A . Understanding helicases as a means of virus control. Curr Pharm Des. 2006; 12(11):1315-38. PMC: 3571686. DOI: 10.2174/138161206776361147. View

15.

Leipe D, Wolf Y, Koonin E, Aravind L . Classification and evolution of P-loop GTPases and related ATPases. J Mol Biol. 2002; 317(1):41-72. DOI: 10.1006/jmbi.2001.5378. View

16.

Seidel R, Bloom J, Dekker C, Szczelkun M . Motor step size and ATP coupling efficiency of the dsDNA translocase EcoR124I. EMBO J. 2008; 27(9):1388-98. PMC: 2291450. DOI: 10.1038/emboj.2008.69. View

17.

Durr H, Korner C, Muller M, Hickmann V, Hopfner K . X-ray structures of the Sulfolobus solfataricus SWI2/SNF2 ATPase core and its complex with DNA. Cell. 2005; 121(3):363-73. DOI: 10.1016/j.cell.2005.03.026. View

18.

Chu W, Hickson I . RecQ helicases: multifunctional genome caretakers. Nat Rev Cancer. 2009; 9(9):644-54. DOI: 10.1038/nrc2682. View

19.

Schlee M, Roth A, Hornung V, Hagmann C, Wimmenauer V, Barchet W . Recognition of 5' triphosphate by RIG-I helicase requires short blunt double-stranded RNA as contained in panhandle of negative-strand virus. Immunity. 2009; 31(1):25-34. PMC: 2824854. DOI: 10.1016/j.immuni.2009.05.008. View

20.

Yang Q, Jankowsky E . The DEAD-box protein Ded1 unwinds RNA duplexes by a mode distinct from translocating helicases. Nat Struct Mol Biol. 2006; 13(11):981-6. DOI: 10.1038/nsmb1165. View