Structures of the double-ring AAA ATPase Pex1-Pex6 involved in peroxisome biogenesis

Abstract

The Pex1 and Pex6 proteins are members of the AAA family of ATPases and are involved in peroxisome biogenesis. Recently, cryo-electron microscopy structures of the Pex1-Pex6 complex in different nucleotide states have been determined. This Structural Snapshot describes the structural features of the complex and their implications for its function, as well as questions that still await answers.

Keywords: AAA ATPases; Pex1-Pex6 complex; cryo-electron microscopy; peroxisome biogenesis; single-particle analysis.

Fig. 1. Cryo-EM structure of the Pex1/Pex6 complex

(A) Models of Pex1 and Pex6 were fitted into the density map (grey envelope) determined in the presence of ATPγS without symmetry imposed [22]. Shown is a top view with the D1 domains colored in blue and the N domains in brown. (B) Magnified view of the N domains in (A). The N domains are distinguished by different colors. (C) As in (A), but side view and including the D2 ring (purple). (D) Magnified view of the N domains in (C), colored as in (B).

Fig. 2. Symmetry of the D1 and D2 rings

The D1 ring is symmetric, while the D2 ring shows pairs of Pex1/Pex6 ATPase domains with varying spacing. The arrows indicate large gaps adjacent to one of the pairs.

Fig. 3. Structural elements of the D2 ring

(A) Top view of the D2 ring with homology models fitted into the density map. (B) Top view of the D2 ring with secondary structure elements shown in the central region. (C) A side view shows that the two helices of the Pex1/Pex6 pair in the front tilt down by ~35°. For clarity, the helix pair of the Pex6 subunit in the back is not shown. The angles were measured between one of the helices of the Pex6 subunit and the plane of the D2 ring. (D) Top view of the D2 ring showing secondary structure elements in the lateral region of the D2 ring. For clarity, only the structural elements of the Pex6 subunits are shown. (E) The side view shows that the long helix of the Pex6 subunit in the front tilts upwards, contacting the D1 ring at the position indicated by an asterisk.

Fig. 4. Model for polypeptide chain movement by Pex1/Pex6

A polypeptide chain moves through the D1 ring into the D2 ring. Pairs of Pex1/Pex6 ATPase domains in the D2 ring undergo a tilting motion in response to ATP hydrolysis, dragging the polypeptide chain through the central pore. At any given moment, one of the Pex1/Pex6 pair is tilted (shown in black), while the other two pairs are not (shown in grey). The tilting motion occurs in a circular manner around the ring.