Crystal structure of UAP56, a DExD/H-box protein involved in pre-mRNA splicing and mRNA export.
UAP56 is an essential eukaryotic pre-mRNA splicing factor and mRNA export factor. The mechanisms of its functions are not well understood. We determined the crystal structures of the N- and C-terminal domains of human UAP56 (comprising 90% of the full-length UAP56) at 1.9 A resolution. The two domains each have a RecA-like fold and are connected by a flexible linker. The overall fold of each domain is highly similar to the corresponding domains of eIF4A (a prototypic DExD/H-box protein), with differences at the loops and termini. This structural similarity suggests that UAP56 is likely to possess ATPase and helicase activity similar to eIF4A. The NTP binding pocket of UAP56 is occupied by a citrate ion, mimicking the phosphates of NTP and retaining the P loop in an open conformation. The crystal structure of the N-terminal domain of UAP56 also reveals a dimer interface that is potentially important for UAP56's function.
Department of Biochemistry and Molecular Genetics, University of Colorado Health Sciences Center, Aurora, Colorado 80045, USA. rui.zhao@uchsc.edu
Rui
R
Zhao
Jingping
J
Shen
Michael R
MR
Green
Margaret
M
MacMorris
Thomas
T
Blumenthal
D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D053487:DEAD-box RNA Helicases; D039601:Eukaryotic Initiation Factor-4A / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D020365:RNA Helicases / Q000737:chemistry*; D012326:RNA Splicing / Q000235:genetics*; D034443:RNA Transport / Q000502:physiology*; D017386:Sequence Homology, Amino Acid
D039601:Eukaryotic Initiation Factor-4A; C487886:DDX39B protein, human; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases