"Structural Evidence for Consecutive Hel308-Like Modules in the Spliceo" by L. Zhang, T. Xu et al.
 

Document Type

Post-Print

Publication Date

7-2009

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.

DOI

10.1038/nsmb.1625

Publisher

Springer Nature

Publication Information

Nature Structural and Molecular Biology

Plum Print visual indicator of research metrics
PlumX Metrics
  • Citations
    • Citation Indexes: 84
    • Patent Family Citations: 6
  • Usage
    • Downloads: 158
    • Abstract Views: 3
  • Captures
    • Readers: 61
see details

Included in

Chemistry Commons

Share

COinS