Common Design Principles in the Spliceosomal RNA Helicase Brr2 and in the Hel308 DNA Helicase
Common Design Principles in the Spliceosomal RNA Helicase Brr2 and in the Hel308 DNA Helicase
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DOI：
10.1016/j.molcel.2009.08.006
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发表时间：
2009-08-28
期刊：
影响因子：
16
通讯作者：
Wahl, Markus C.
中科院分区：
文献类型：
--
作者：
Pena, Vladimir;Jovin, Sina Mozaffari;Wahl, Markus C.
Brr2 is a unique DExD/H box protein required for catalytic activation and disassembly of the spliceosome. It contains two tandem helicase cassettes that both comprise dual RecA-like domains and a noncanonical Sec63 unit. The latter may bestow the enzyme with unique properties. We have determined crystal structures of the C-terminal Sec63 unit of yeast Brr2, revealing three domains, two of which resemble functional modules of a DNA helicase, Hel308, despite lacking significant sequence similarity. This structural similarity together with sequence conservation between the enzymes throughout the RecA-like domains and a winged helix domain allowed us to devise a structural model of the N-terminal active cassette of Brr2. We consolidated the model by rational mutagenesis combined with splicing and U4/U6 di-snRNA unwinding assays, highlighting how the RecA-like domains and the Sec63 unit form a functional entity that appears suitable for unidirectional and processive RNA duplex unwinding during spliceosome activation and disassembly.
