4xw3
Crystal structure of the SPRY domain of the human DEAD-box protein DDX1
Structural highlights
FunctionDDX1_HUMAN Acts as an ATP-dependent RNA helicase, able to unwind both RNA-RNA and RNA-DNA duplexes. Possesses 5' single-stranded RNA overhang nuclease activity. Possesses ATPase activity on various RNA, but not DNA polynucleotides. May play a role in RNA clearance at DNA double-strand breaks (DSBs), thereby facilitating the template-guided repair of transcriptionally active regions of the genome. Together with RELA, acts as a coactivator to enhance NF-kappa-B-mediated transcriptional activation. Acts as a positive transcriptional regulator of cyclin CCND2 expression. Binds to the cyclin CCND2 promoter region. Associates with chromatin at the NF-kappa-B promoter region via association with RELA. Binds to poly(A) RNA. May be involved in 3'-end cleavage and polyadenylation of pre-mRNAs. Component of the tRNA-splicing ligase complex required to facilitate the enzymatic turnover of catalytic subunit RTCB: together with archease (ZBTB8OS), acts by facilitating the guanylylation of RTCB, a key intermediate step in tRNA ligation (PubMed:24870230). Component of a multi-helicase-TICAM1 complex that acts as a cytoplasmic sensor of viral double-stranded RNA (dsRNA) and plays a role in the activation of a cascade of antiviral responses including the induction of pro-inflammatory cytokines via the adapter molecule TICAM1. Specifically binds (via helicase ATP-binding domain) on both short and long poly(I:C) dsRNA (By similarity).[UniProtKB:Q91VR5][1] [2] [3] [4] [5] [6] (Microbial infection) Required for HIV-1 Rev function as well as for HIV-1 and coronavirus IBV replication. Binds to the RRE sequence of HIV-1 mRNAs.[7] (Microbial infection) Required for Coronavirus IBV replication.[8] Publication Abstract from PubMedThe human RNA helicase DDX1 in the DEAD-box family plays an important role in RNA processing and has been associated with HIV-1 replication and tumour progression. Whereas previously described DEAD-box proteins have a structurally conserved core, DDX1 shows a unique structural feature: a large SPRY-domain insertion in its RecA-like consensus fold. SPRY domains are known to function as protein-protein interaction platforms. Here, the crystal structure of the SPRY domain of human DDX1 (hDSPRY) is reported at 2.0 A resolution. The structure reveals two layers of concave, antiparallel beta-sheets that stack onto each other and a third beta-sheet beneath the beta-sandwich. A comparison with SPRY-domain structures from other eukaryotic proteins showed that the general beta-sandwich fold is conserved; however, differences were detected in the loop regions, which were identified in other SPRY domains to be essential for interaction with cognate partners. In contrast, in hDSPRY these loop regions are not strictly conserved across species. Interestingly, though, a conserved patch of positive surface charge is found that may replace the connecting loops as a protein-protein interaction surface. The data presented here comprise the first structural information on DDX1 and provide insights into the unique domain architecture of this DEAD-box protein. By providing the structure of a putative interaction domain of DDX1, this work will serve as a basis for further studies of the interaction network within the hetero-oligomeric complexes of DDX1 and of its recruitment to the HIV-1 Rev protein as a viral replication factor. Structure of the SPRY domain of the human RNA helicase DDX1, a putative interaction platform within a DEAD-box protein.,Kellner JN, Meinhart A Acta Crystallogr F Struct Biol Commun. 2015 Sep 1;71(Pt 9):1176-88. doi:, 10.1107/S2053230X15013709. Epub 2015 Aug 25. PMID:26323305[9] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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