Structures overview
fig 1 - core recA-like domains
fig 2 - recA-like domain interaction and Q motif
fig 3 - protrusions from both recA-like domains
fig 4 - linker spanning between domains
fig 5 - brace inside protrusion 2
core recA-like domains

At the core of all SF1 and SF2 helicase proteins are a pair of recA-related domains (fig 1), each consisting of a 5-strand beta sheet decorated by alpha helices on either face 1, 2. The ATP hydrolysis site is located at the base of the cleft formed by the inter-domain association, primarily mediated by Walker motifs A and B (helicase motifs I and II) in recA-like domain 1 and an ‘arginine finger’ contributed by motif VI of recA-like domain 2 2, 3.

ATP-driven mechanism

ATP hydrolysis appears to cause a change in the relative orientations of the two domains of the helicase proteins, involving the concerted action of the ATP binding and other ‘sensor’ residues such as the TxGx motif (ie conserved block A) and motif III. The distinction between superfamilies 1 and 2 is based on the detailed interactions involved in nucleic acid substrate and ATP binding, and how these are interlinked to direct the mechanical changes in the bound nucleic acid driven by ATP hydrolysis 4, 5. These distinctions are reflected in subtle differences in the conserved helicase motifs which gave rise to the original classification of superfamilies by Gorbalenya and Koonin 6.

The Q motif (fig 2) is an additional structure found in many SF2 proteins, including the Snf2 family, which makes further interactions with ATP 7.

unique Snf2 family structures

The most remarkable feature of the Snf2 family structures compared to other known SF2 members are several additional structural elements grafted onto the core helicase structure. These comprise:

  • antiparallel alpha helical protrusions from both recA-like domains 1 and 2 (fig 3)
  • a structured linker between the recA-like domains (fig 4)
  • a triangular brace packed against the domain 2 alpha helical protrusion (fig 5)

The two helical protrusions and linker are all encoded within the enlarged span between motifs III and IV. The triangular brace is encoded immediately downstream of motif VI.

insertion sites

A major insertion site is also located behind protrusion 2.

1: Hall, M. C. and S. W. Matson (1999). Helicase motifs: the engine that powers DNA unwinding. Mol Microbiol 34(5): 867-77. PubMed
2: Caruthers, J. M. and D. B. McKay (2002). Helicase structure and mechanism. Curr Opin Struct Biol 12(1): 123-33. PubMed
3: Ye, J., A. R. Osborne, et al. (2004). RecA-like motor ATPases--lessons from structures. Biochim Biophys Acta 1659(1): 1-18. PubMed
4: Korolev, S., N. Yao, et al. (1998). Comparisons between the structures of HCV and Rep helicases reveal structural similarities between SF1 and SF2 super-families of helicases. Protein Sci 7(3): 605-10. PubMed
5: Singleton, M. R. and D. B. Wigley (2002). Modularity and specialization in superfamily 1 and 2 helicases. J Bacteriol 184(7): 1819-26. PubMed
6: Gorbalenya, A. E. and E. V. Koonin (1993). Helicases: amino acid sequence comparisons and structure-function relationship. Curr Opin Struct Biol 3(4): 419-429 (not in PubMed)
7: Tanner, N. K., O. Cordin, et al. (2003). The Q motif: a newly identified motif in DEAD box helicases may regulate ATP binding and hydrolysis. Mol Cell 11(1): 127-38. PubMed