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 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.
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.
A major insertion site is also located behind protrusion 2.