4pj3

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Structural insight into the function and evolution of the spliceosomal helicase Aquarius, Structure of Aquarius in complex with AMPPNPStructural insight into the function and evolution of the spliceosomal helicase Aquarius, Structure of Aquarius in complex with AMPPNP

Structural highlights

4pj3 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.3Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

AQR_HUMAN Intron-binding spliceosomal protein required to link pre-mRNA splicing and snoRNP (small nucleolar ribonucleoprotein) biogenesis. Plays a key role in position-dependent assembly of intron-encoded box C/D small snoRNP, splicing being required for snoRNP assembly. May act by helping the folding of the snoRNA sequence. Binds to intron of pre-mRNAs in a sequence-independent manner, contacting the region between snoRNA and the branchpoint of introns (40 nucleotides upstream of the branchpoint) during the late stages of splicing.[1]

Publication Abstract from PubMed

Aquarius is a multifunctional putative RNA helicase that binds precursor-mRNA introns at a defined position. Here we report the crystal structure of human Aquarius, revealing a central RNA helicase core and several unique accessory domains, including an ARM-repeat domain. We show that Aquarius is integrated into spliceosomes as part of a pentameric intron-binding complex (IBC) that, together with the ARM domain, cross-links to U2 snRNP proteins within activated spliceosomes; this suggests that the latter aid in positioning Aquarius on the intron. Aquarius's ARM domain is essential for IBC formation, thus indicating that it has a key protein-protein-scaffolding role. Finally, we provide evidence that Aquarius is required for efficient precursor-mRNA splicing in vitro. Our findings highlight the remarkable structural adaptations of a helicase to achieve position-specific recruitment to a ribonucleoprotein complex and reveal a new building block of the human spliceosome.

The RNA helicase Aquarius exhibits structural adaptations mediating its recruitment to spliceosomes.,De I, Bessonov S, Hofele R, Dos Santos K, Will CL, Urlaub H, Luhrmann R, Pena V Nat Struct Mol Biol. 2015 Feb;22(2):138-44. doi: 10.1038/nsmb.2951. Epub 2015 Jan, 19. PMID:25599396[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. Hirose T, Ideue T, Nagai M, Hagiwara M, Shu MD, Steitz JA. A spliceosomal intron binding protein, IBP160, links position-dependent assembly of intron-encoded box C/D snoRNP to pre-mRNA splicing. Mol Cell. 2006 Sep 1;23(5):673-84. PMID:16949364 doi:http://dx.doi.org/S1097-2765(06)00491-6
  2. De I, Bessonov S, Hofele R, Dos Santos K, Will CL, Urlaub H, Luhrmann R, Pena V. The RNA helicase Aquarius exhibits structural adaptations mediating its recruitment to spliceosomes. Nat Struct Mol Biol. 2015 Feb;22(2):138-44. doi: 10.1038/nsmb.2951. Epub 2015 Jan, 19. PMID:25599396 doi:http://dx.doi.org/10.1038/nsmb.2951

4pj3, resolution 2.30Å

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OCA