Structural highlights
Function
[CLP1_YEAST] Component of the cleavage factor IA (CFIA) complex, which is involved in the endonucleolytic cleavage during polyadenylation-dependent pre-mRNA 3'-end formation and cooperates with the cleavage factor NAB4/CFIB and the cleavage and polyadenylation factor (CPF) complex.[1] [PCF11_YEAST] Component of the cleavage factor IA (CFIA) complex, which is involved in the endonucleolytic cleavage during polyadenylation-dependent pre-mRNA 3'-end formation and cooperates with cleavage factor NAB4/CFIB and the cleavage and polyadenylation factor (CPF) complex. Independently involved in RNA polymerase II transcript termination. Binds RNA. Seems to bridge RNA polymerase II and the native transcript and may be involved in dismantling the RNA polymerase II elongation complex.[2] [3]
Publication Abstract from PubMed
RNA-specific polynucleotide kinases of the Clp1 subfamily are key components of various RNA maturation pathways. However, the structural basis explaining their substrate specificity and the enzymatic mechanism is elusive. Here, we report crystal structures of Clp1 from Caenorhabditis elegans (ceClp1) in a number of nucleotide- and RNA-bound states along the reaction pathway. The combined structural and biochemical analysis of ceClp1 elucidates the RNA specificity and lets us derive a general model for enzyme catalysis of RNA-specific polynucleotide kinases. We identified an RNA binding motif referred to as "clasp" as well as a conformational switch that involves the essential Walker A lysine (Lys127) and regulates the enzymatic activity of ceClp1. Structural comparison with other P loop proteins, such as kinases, adenosine triphosphatases (ATPases), and guanosine triphosphatases (GTPases), suggests that the observed conformational switch of the Walker A lysine is a broadly relevant mechanistic feature.
RNA specificity and regulation of catalysis in the eukaryotic polynucleotide kinase clp1.,Dikfidan A, Loll B, Zeymer C, Magler I, Clausen T, Meinhart A Mol Cell. 2014 Jun 19;54(6):975-86. doi: 10.1016/j.molcel.2014.04.005. Epub 2014 , May 8. PMID:24813946[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Gross S, Moore C. Five subunits are required for reconstitution of the cleavage and polyadenylation activities of Saccharomyces cerevisiae cleavage factor I. Proc Natl Acad Sci U S A. 2001 May 22;98(11):6080-5. Epub 2001 May 8. PMID:11344258 doi:http://dx.doi.org/10.1073/pnas.101046598
- ↑ Gross S, Moore C. Five subunits are required for reconstitution of the cleavage and polyadenylation activities of Saccharomyces cerevisiae cleavage factor I. Proc Natl Acad Sci U S A. 2001 May 22;98(11):6080-5. Epub 2001 May 8. PMID:11344258 doi:http://dx.doi.org/10.1073/pnas.101046598
- ↑ Zhang Z, Fu J, Gilmour DS. CTD-dependent dismantling of the RNA polymerase II elongation complex by the pre-mRNA 3'-end processing factor, Pcf11. Genes Dev. 2005 Jul 1;19(13):1572-80. PMID:15998810 doi:http://dx.doi.org/19/13/1572
- ↑ Dikfidan A, Loll B, Zeymer C, Magler I, Clausen T, Meinhart A. RNA specificity and regulation of catalysis in the eukaryotic polynucleotide kinase clp1. Mol Cell. 2014 Jun 19;54(6):975-86. doi: 10.1016/j.molcel.2014.04.005. Epub 2014 , May 8. PMID:24813946 doi:http://dx.doi.org/10.1016/j.molcel.2014.04.005
