Human DEAD-box RNA helicase DDX25, Helicase domain

The DExD/H family of RNA-binding helicases consists of a large group of proteins that are involved in general cellular RNA-metabolism such as transcription, splicing, RNA nucleocytoplasmatic transport, translation and ribosome biogenesis. All DExD/H helicases are defined by their ability to bind and hydrolyse ATP and are generally believed to unwind RNA-secondary structure or assist in the folding of RNA/RNP complexes thus acting as RNA chaperones. Proteins in this family consist of two domains: an N-terminal domain with the conserved DExD/H motif and a C-terminal helicase domain. Altogether there are at least eight conserved motifs that are involved in coordination and hydrolysis of ATP and binding of RNA.

DDX25 is a DEAD-box helicase that is transcriptionally upregulated by human chorionic gonadotropin via cyclic-AMP and androgen formation in testis. DDX25 is essential for spermatogenesis since male mice with a mutation in the DDX25 gene are sterile and it may be linked to human spermatogenesis impairment. DDX25 is also regulated at the translation level; different ATG-codons are used depending on cell-type yielding DDX25-proteins of three varying lengths. It has been suggested that DDX25 is a mRNA-binding protein that is involved in posttranscriptional events that result in the translation of proteins that are required for spermatogenesis.

We have solved the structure of the DDX25 helicase-domain at 2.8 Å. This domain contains the conserved motifs IV, V and VI that are suggested to be involved in RNA-binding and coordination of ATPase activities. It also contains amino acids that are unique to DDX25 at the C-terminus of the protein.