Abstract:
:Brr2 is a DExD/H-box helicase responsible for U4/U6 unwinding during spliceosomal activation. Brr2 contains two helicase-like domains, each of which is followed by a Sec63 domain with unknown function. We determined the crystal structure of the second Sec63 domain, which unexpectedly resembles domains 4 and 5 of DNA helicase Hel308. This, together with sequence similarities between Brr2's helicase-like domains and domains 1-3 of Hel308, led us to hypothesize that Brr2 contains two consecutive Hel308-like modules (Hel308-I and Hel308-II). Our structural model and mutagenesis data suggest that Brr2 shares a similar helicase mechanism with Hel308. We demonstrate that Hel308-II interacts with Prp8 and Snu114 in vitro and in vivo. We further find that the C-terminal region of Prp8 (Prp8-CTR) facilitates the binding of the Brr2-Prp8-CTR complex to U4/U6. Our results have important implications for the mechanism and regulation of Brr2's activity in splicing.
journal_name
Nat Struct Mol Bioljournal_title
Nature structural & molecular biologyauthors
Zhang L,Xu T,Maeder C,Bud LO,Shanks J,Nix J,Guthrie C,Pleiss JA,Zhao Rdoi
10.1038/nsmb.1625subject
Has Abstractpub_date
2009-07-01 00:00:00pages
731-9issue
7eissn
1545-9993issn
1545-9985pii
nsmb.1625journal_volume
16pub_type
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