期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 105, 期 37, 页码 13817-13822出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0805960105
关键词
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资金
- Offices of Biological and Environmental Research
- Basic Energy Sciences of the U.S.
- Department of Energy and the National Center for Research Resources of the National Institutes of Health
- National Science Foundation [MCB-0718802]
- Thorkildsen postdoctoral
- American Heart Association
Prp8 stands out among hundreds of splicing factors as a key regulator of spliceosome activation and a potential cofactor of the splicing reaction. We present here the crystal structure of a 274-residue domain (residues 1,822-2,095) near the C terminus of Saccharomyces cerevisiae Prp8. The most striking feature of this domain is a beta-hairpin finger protruding out of the protein (hence, this domain will be referred to as the beta-finger domain), resembling many globular ribosomal proteins with protruding extensions. Mutations throughout the beta-finger change the conformational equilibrium between the first and the second catalytic step. Mutations at the base of the beta-finger affect U4/U6 unwinding-mediated spliceosome activation. Prp8 may insert its beta-finger into the first-step complex (U2/U5/U6/pre-mRNA) or U4/U6.U5 tri-snRNP and stabilize these complexes. Mutations on the beta-finger likely alter these interactions, leading to the observed mutant phenotypes. Our results suggest a possible mechanism of how Prp8 regulates spliceosome activation. These results also demonstrate an analogy between a spliceosomal protein and ribosomal proteins that insert extensions into folded rRNAs and stabilize the ribosome.
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