| Structural highlights
Function
PRP5_YEAST ATP-dependent RNA helicase involved spliceosome assembly and in nuclear splicing. Catalyzes an ATP-dependent conformational change of U2 snRNP. Bridges U1 and U2 snRNPs and enables stable U2 snRNP association with intron RNA.[1] [2] [3] [4] [5] [6] [7] [8]
Publication Abstract from PubMed
The DEAD-box adenosine triphosphatase (ATPase) Prp5p facilitates U2 small nuclear ribonucleoprotein particle (snRNP) binding to the intron branch site region during spliceosome assembly. We present crystal structures of S. cerevisiae Prp5p alone and in complex with ADP at 2.12 A and 1.95 A resolution. The three-dimensional packing of Prp5p subdomains differs strikingly from that so far observed in other DEAD-box proteins: two RecA-like subdomains adopt an "open state" conformation stabilized by extensive interactions involving sequences that flank the two subdomains. This conformation is distinct from that required for ATP hydrolysis. Consistent with this, Prp5p mutations that destabilize interdomain interactions exhibited increased ATPase activity in vitro and inhibited splicing of suboptimal branch site substrates in vivo, whereas restoration of interdomain interactions reversed these effects. We conclude that the Prp5p open state conformation is biologically relevant and that disruption of the interdomain interaction facilitates a large-scale conformational change of Prp5p during U2 snRNP-branch site recognition.
Crystal structure of Prp5p reveals interdomain interactions that impact spliceosome assembly.,Zhang ZM, Yang F, Zhang J, Tang Q, Li J, Gu J, Zhou J, Xu YZ Cell Rep. 2013 Dec 12;5(5):1269-78. doi: 10.1016/j.celrep.2013.10.047. Epub 2013 , Nov 27. PMID:24290758[9]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ruby SW, Chang TH, Abelson J. Four yeast spliceosomal proteins (PRP5, PRP9, PRP11, and PRP21) interact to promote U2 snRNP binding to pre-mRNA. Genes Dev. 1993 Oct;7(10):1909-25. PMID:8405998
- ↑ Wells SE, Ares M Jr. Interactions between highly conserved U2 small nuclear RNA structures and Prp5p, Prp9p, Prp11p, and Prp21p proteins are required to ensure integrity of the U2 small nuclear ribonucleoprotein in Saccharomyces cerevisiae. Mol Cell Biol. 1994 Sep;14(9):6337-49. PMID:8065365
- ↑ O'Day CL, Dalbadie-McFarland G, Abelson J. The Saccharomyces cerevisiae Prp5 protein has RNA-dependent ATPase activity with specificity for U2 small nuclear RNA. J Biol Chem. 1996 Dec 27;271(52):33261-7. PMID:8969184
- ↑ Wiest DK, O'Day CL, Abelson J. In vitro studies of the Prp9.Prp11.Prp21 complex indicate a pathway for U2 small nuclear ribonucleoprotein activation. J Biol Chem. 1996 Dec 27;271(52):33268-76. PMID:8969185
- ↑ Yan D, Ares M Jr. Invariant U2 RNA sequences bordering the branchpoint recognition region are essential for interaction with yeast SF3a and SF3b subunits. Mol Cell Biol. 1996 Mar;16(3):818-28. PMID:8622683
- ↑ Abu Dayyeh BK, Quan TK, Castro M, Ruby SW. Probing interactions between the U2 small nuclear ribonucleoprotein and the DEAD-box protein, Prp5. J Biol Chem. 2002 Jun 7;277(23):20221-33. Epub 2002 Apr 1. PMID:11927574 doi:http://dx.doi.org/10.1074/jbc.M109553200
- ↑ Perriman R, Barta I, Voeltz GK, Abelson J, Ares M Jr. ATP requirement for Prp5p function is determined by Cus2p and the structure of U2 small nuclear RNA. Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):13857-62. Epub 2003 Nov 10. PMID:14610285 doi:http://dx.doi.org/10.1073/pnas.2036312100
- ↑ Wang Q, He J, Lynn B, Rymond BC. Interactions of the yeast SF3b splicing factor. Mol Cell Biol. 2005 Dec;25(24):10745-54. PMID:16314500 doi:http://dx.doi.org/25/24/10745
- ↑ Zhang ZM, Yang F, Zhang J, Tang Q, Li J, Gu J, Zhou J, Xu YZ. Crystal structure of Prp5p reveals interdomain interactions that impact spliceosome assembly. Cell Rep. 2013 Dec 12;5(5):1269-78. doi: 10.1016/j.celrep.2013.10.047. Epub 2013 , Nov 27. PMID:24290758 doi:http://dx.doi.org/10.1016/j.celrep.2013.10.047
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