Article abstract
Nature Structural & Molecular Biology 16, 740 - 746 (2009)
Published online: 28 May 2009 | doi:10.1038/nsmb.1624
Structure of a functional ribonucleoprotein pseudouridine synthase bound to a substrate RNA
Bo Liang1, Jing Zhou2, Elliot Kahen2, Rebecca M Terns3, Michael P Terns3 & Hong Li1,2
Abstract
Box H/ACA small nucleolar and Cajal body ribonucleoprotein particles comprise the most complex pseudouridine synthases and are essential for ribosome and spliceosome maturation. The multistep and multicomponent-mediated enzyme mechanism remains only partially understood. Here we report a crystal structure at 2.35 Å of a substrate-bound functional archaeal enzyme containing three of the four proteins, Cbf5, Nop10 and L7Ae, and a box H/ACA RNA that reveals detailed information about the protein-only active site. The substrate RNA, containing 5-fluorouridine at the modification position, is fully docked and catalytically rearranged by the enzyme in a manner similar to that seen in two stand-alone pseudouridine synthases. Structural analysis provides a mechanism for plasticity in the diversity of guide RNA sequences used and identifies a substrate-anchoring loop of Cbf5 that also interacts with Gar1 in unliganded structures. Activity analyses of mutated proteins and RNAs support the structural findings and further suggest a role of the Cbf5 loop in regulation of enzyme activity.
- Institute of Molecular Biophysics, Tallahassee, Florida, USA.
- Department of Chemistry and Biochemistry, Florida State University, Tallahassee, Florida, USA.
- Department of Biochemistry and Molecular Biology, University of Georgia at Athens, Athens, Georgia, USA.
Correspondence to: Hong Li1,2 e-mail: hong.li@fsu.edu
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