Display Settings:


Send to:

Choose Destination
See comment in PubMed Commons below
Proc Natl Acad Sci U S A. 2004 Dec 21;101(51):17628-33. Epub 2004 Dec 7.

Crystal structure of the human ATP-dependent splicing and export factor UAP56.

Author information

  • 1W. M. Keck Structural Biology Laboratory, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.


Pre-mRNA splicing requires the function of a number of RNA-dependent ATPases/helicases, yet no three-dimensional structure of any spliceosomal ATPases/helicases is known. The highly conserved DECD-box protein UAP56/Sub2 is an essential splicing factor that is also important for mRNA export. The expected ATPase/helicase activity appears to be essential for the UAP56/Sub2 functions. Here, we show that purified human UAP56 is an active RNA-dependent ATPase, and we also report the crystal structures of UAP56 alone and in complex with ADP, as well as a DECD to DEAD mutant. The structures reveal a unique spatial arrangement of the two conserved helicase domains, and ADP-binding induces significant conformational changes of key residues in the ATP-binding pocket. Our structural analyses suggest a specific protein-RNA displacement model of UAP56/Sub2. The detailed structural information provides important mechanistic insights into the splicing function of UAP56/Sub2. The structures also will be useful for the analysis of other spliceosomal DExD-box ATPases/helicases.

[PubMed - indexed for MEDLINE]
Free PMC Article

Images from this publication.See all images (5)Free text

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 5.
Fig. 4.
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk