Regulation of the Dbp5 ATPase cycle in mRNP remodeling at the nuclear pore: a lively new paradigm for DEAD-box proteins

Abstract

It is commonly assumed that all DEAD-box ATPases function via a shared mechanism, since this is the case for the few proteins characterized thus far. Hodge and colleagues (pp. 1052-1064) and Noble and colleagues (pp. 1065-1077) now describe a novel model for Dbp5's ATPase cycle in mRNA (messenger RNA)/protein complex (mRNP) remodeling during nuclear export. Notably, unlike other DEAD-box proteins, Dbp5 uses a conformational change distinct from ATP hydrolysis for its activity and requires an ADP release factor to reset its ATPase cycle.

Figure 1.

Dbp5 structural model. (A) Schematic representation of yeast Dbp5. The N-terminal region of Dbp5 does not contain any known motifs and its structure is unknown. The two domains of the conserved helicase core are shown in blue and purple. The nine motifs conserved among DEAD-box proteins are shown in yellow boxes within the two RecA-like domains. The Q motif contacts the adenine base of ATP; motifs I, II, and VI contact the phosphate groups of ATP; and motifs Ia, Ib, IV, and V contact the RNA backbone. Motif II contains the conserved D-E-A-D residues for which the family of proteins is named. (B) Cartoon of domain arrangement of Dbp5 bound to ATP and RNA. The structure of the gray N-terminal region of Dbp5 is unknown. A flexible linker connects the two RecA-like domains. (C) Cartoon showing which faces of Dbp5 bind Gle1-IP₆ and Nup159. Both have been shown in vitro to simultaneously bind Dbp5 in the presence of ADP and absence of RNA.

Figure 2.

Simplified model of Dbp5 ATPase cycle. (1) The cycle begins with a nucleotide-free Dbp5, which is ATPase-repressed by its NTD. (2) Next, Gle1-IP₆ binding to Dbp5 stimulates it to bind ATP. (3) Then, an mRNP binds the Dbp5–Gle1-IP₆–ATP complex. After ATP hydrolysis, Dbp5 changes its conformation and releases the remodeled mRNA. (4) Nup159 binds to Dbp5 and stimulates it to release ADP.