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

Shi, H., Cordin, O., Minder, C. M., Linder, P., Xu, R. M. (December 2004) Crystal structure of the human ATP-dependent splicing and export factor UAP56. Proc Natl Acad Sci U S A, 101 (51). pp. 17628-33. ISSN 0027-8424 (Print)

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DOI: 10.1073/pnas.0408172101


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.

Item Type: Paper
Uncontrolled Keywords: Adenosine Diphosphate metabolism Adenosine Triphosphatases chemistry genetics/metabolism Adenosine Triphosphate metabolism Amino Acid Motifs Amino Acid Sequence Binding Sites Crystallography X-Ray DEAD-box RNA Helicases Humans Models Molecular Molecular Sequence Data Mutation genetics Protein Conformation RNA metabolism RNA Helicases chemistry genetics metabolism Sequence Alignment
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > pre-mRNA
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > splicing factor
CSHL Authors:
Communities: CSHL labs > Xu lab
Depositing User: CSHL Librarian
Date: 21 December 2004
Date Deposited: 26 Jan 2012 15:17
Last Modified: 09 Nov 2017 17:01
PMCID: PMC539749
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