7dcr
From Proteopedia
cryo-EM structure of the DEAH-box helicase Prp2 in complex with its coactivator Spp2
Structural highlights
FunctionPRP2_YEAST Involved in pre-mRNA splicing. Is required together with ATP and at least one other factor, for the first cleavage-ligation reaction. Functions as a molecular motor in the activation of the precatalytic spliceosome for the first transesterification reaction of pre-mRNA splicing by hydrolyzing ATP to cause the activation of the spliceosome without the occurrence of splicing. Capable of hydrolyzing nucleoside triphosphates in the presence of single-stranded RNAs such as poly(U).[1] [2] [3] [4] [5] Publication Abstract from PubMedSpliceosome remodeling, executed by conserved ATPase/helicases including Prp2, enables pre-mRNA splicing. However, the structural basis for the function of the ATPase/helicases remains poorly understood. Here, we report atomic structures of Prp2 in isolation, Prp2 complexed with its coactivator Spp2, and Prp2-loaded activated spliceosome, and results of structure-guided biochemical analysis. Prp2 weakly associates with the spliceosome and cannot function without Spp2, which stably associates with Prp2 and anchors on the spliceosome, thus tethering Prp2 to the activated spliceosome and allowing Prp2 to function. Pre-mRNA is loaded into a featured channel between the N- and C-halves of Prp2, where Leu536 from the N-half and Arg844 from the C-half prevent backward sliding of pre-mRNA toward its 5'-end. ATP binding and hydrolysis trigger inter-domain movement in Prp2, which drives unidirectional step-wise translocation of pre-mRNA toward its 3'-end. These conserved mechanisms explain the coupling of spliceosome remodeling to pre-mRNA splicing. Mechanism of spliceosome remodeling by the ATPase/helicase Prp2 and its coactivator Spp2.,Bai R, Wan R, Yan C, Jia Q, Lei J, Shi Y Science. 2020 Nov 26. pii: science.abe8863. doi: 10.1126/science.abe8863. PMID:33243853[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Large Structures | Saccharomyces cerevisiae | Bai R | Jia Q | Lei J | Shi Y | Wan R | Yan C | Zhang P
