DEAD-box RNA-helicase DDX19 in complex with ADP

Human DEAD-box RNA-helicase DDX19 in complex with ADP (3ews)

About this Structure

3EWS is a 2 chains structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

The crystallographic asymmetric unit of the solved structure contains 2 monomers of DDX19 (residues 53-472 of 479 for both molecules) complexed with the nucleotide ADP.

The biological molecule is a single-chain DDX19 monomer. Fancy, high-quality cartoons on/off.

DDX19 is made of 2 RecA-like helicase domains (called the N-terminal ATPase and C-terminal helicase domains in the paper).

• With ADP bound, an N-terminal extension (dark green) is wedged in a cleft between these domains negatively regulating ATPase activity by preventing cleft closure.
• This conformation is presumed to resemble the post-hydrolysis state in which RNA is not bound. It is also referred to as the open state and open cleft conformation.
• This scene is similar to the view in Figure 1a of the paper describing the structure. (This scene is even more similar because Arginine 429, discussed below, is included as in that figure.)

Showing the structure of DDX19 with ADP bound along with the structure where RNA and an ATP analog are bound.

• This overlay clearly illustrates the dramatic shift in the location of the N-terminal extension (dark green).
• This view clearly shows how the N-terminal helix of the extension extends from the RNA-binding site to down near the ATP binding site.

Pre-hydrolysis (RNA and ATP bound) to post-hydrolysis (ADP bound) morph. The placement of the N-terminal extension between the two helicase domains negatively regulates ATPase activity. A morph of the ADP-bound structure transitioning to the structure with a non-hydrolyzable ATP analog and mRNA mimic bound shows the N-terminal extension moving out of the way, closing the cleft to allow formation of a functional ATPase site.

• Of particular note is arginine 429, the so-called arginine finger, that is essential for ATPase activity. In the ADP bound structure arginine 429 is far from the nucleotide-binding site due to the helix of the extension sitting in the cleft.
• Watching arginine 429 during the morph transition illustrates how it is moved to sit near the active site when RNA is bound, enabling ATPase activity.
• Keep in mind the intermediate models, in between the endpoints, are hypothetical.

See also

• Helicase
• 3g0h is human DDX19 with a non-hydrolyzable ATP analog and mRNA mimic bound. It is used in the morphs here and was described in the same article as 3ews.