Snf2 family ATPases and DExx box helicases: differences and unifying concepts from high-resolution crystal structures

Abstract

Proteins with sequence similarity to the yeast Snf2 protein form a large family of ATPases that act to alter the structure of a diverse range of DNA-protein structures including chromatin. Snf2 family enzymes are related in sequence to DExx box helicases, yet they do not possess helicase activity. Recent biochemical and structural studies suggest that the mechanism by which these enzymes act involves ATP-dependent translocation on DNA. Crystal structures suggest that these enzymes travel along the minor groove, a process that can generate the torque or energy in remodelling processes. We review the recent structural and biochemical findings which suggest a common mechanistic basis underlies the action of many of both Snf2 family and DExx box helicases.

Figure 1

Comparison of Structures of Snf2 family enzymes and the RecG helicase. Structural comparison of the S.solfataricus (sso) SSO1653 catalytic domain [cd, (43), the zebrafish (zf) Rad54 cd (68) and T.maritima (tm) RecG (53). The three crystal structures are shown as ribbon models with highlighted secondary structures. DNA molecules bound to SSO1653 and tmRecG are shown as brown ribbon model. The two RecA-like domains (1A: orange, 2A: green) are shared across DExx box ATPases, and form the ATP-binding site in their interface cleft. The location of the ATP-binding site, as well as locations of the seven conserved helicase-related ATPase/DNA-binding motifs (Ia,I,II,III,IV,V,VI) are indicated in tmRecG. The two RecA-like domains interact with additional domains (1B and 2B: blue) that are suggested to convert ATP-driven rearrangements of 1A and 2A into the translocase or DNA unwinding function. For instance, these domains bind to the replication fork substrate in RecG, which is dragged like a plough through DNA by the action of the translocase module. The role of the helical domains of Snf2 family enzymes is not as well understood, but they could play a role in advancing the enzyme by ATP-driven conformational changes. Note that domain 2 of SSO1653 (2A and 2B) is flipped by 180° with respect to more typical conformations found in zfRad54cd and RecG (double arrow). This flip could represent an open conformation during substrate uptake.

Figure 2

Unified mechanism of Snf2 family ATPases and DExx box helicases. Schematic comparison of (A) dsDNA translocases (e.g. Snf2) and (B) ssDNA translocases (e.g. PcrA and NS3 helicases). Both enzyme families contain a conserved RecA-like domain core (orange/green), but differ in other subunits (data not shown). Helicases transport product ssDNA and often contain an upstream DNA unwinding element (grey triangle). In contrast, Snf2 family enzymes also recognize the 5′–3′ strand (blue) and track along the minor groove. Despite many functional differences, however, both enzymes families bind the 3′–5′ strands at an equivalent site across the two RecA-like domains, indicating that ATP-driven conformational changes transport DNA substrates via the 3′–5′ strands in analogous ways (arrows).