Abstract:
: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.
journal_name
Mol Celljournal_title
Molecular cellauthors
Pena V,Jovin SM,Fabrizio P,Orlowski J,Bujnicki JM,Lührmann R,Wahl MCdoi
10.1016/j.molcel.2009.08.006subject
Has Abstractpub_date
2009-08-28 00:00:00pages
454-66issue
4eissn
1097-2765issn
1097-4164pii
S1097-2765(09)00552-8journal_volume
35pub_type
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