3c66
Yeast poly(A) polymerase in complex with Fip1 residues 80-105Yeast poly(A) polymerase in complex with Fip1 residues 80-105
Structural highlights
Function[PAP_YEAST] Polymerase component of the cleavage and polyadenylation factor (CPF) complex, which plays a key role in polyadenylation-dependent pre-mRNA 3'-end formation and cooperates with cleavage factors including the CFIA complex and NAB4/CFIB.[1] [2] [FIP1_YEAST] Polymerase-regulating component of the cleavage and polyadenylation factor (CPF) complex, which plays a key role in polyadenylation-dependent pre-mRNA 3'-end formation and cooperates with cleavage factors including the CFIA complex and NAB4/CFIB. Pre-mRNA polyadenylation factor that directly interacts with poly(A) polymerase PAP1. This inhibits the extension of an oligo(A) primer by limiting access of the RNA substrate to the C-terminal RNA binding domain of PAP1. Seems to tether PAP1 to the cleavage factor I.[3] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedIn yeast, the mRNA processing enzyme poly(A) polymerase is tethered to the much larger 3'-end processing complex via Fip1, a 36 kDa protein of unknown structure. We report the 2.6 A crystal structure of yeast poly(A) polymerase in complex with a peptide containing residues 80-105 of Fip1. The Fip1 peptide binds to the outside surface of the C-terminal domain of the polymerase. On the basis of this structure, we designed a mutant of the polymerase (V498Y, C485R) that is lethal to yeast. The mutant is unable to bind Fip1 but retains full polymerase activity. Fip1 is found in all eukaryotes and serves to connect poly(A) polymerase to pre-mRNA processing complexes in yeast, plants, and mammals. However, the Fip1 sequence is highly divergent, and residues on both Pap1 and Fip1 at the observed interaction surface are poorly conserved. Herein we demonstrate using analytical ultracentrifugation, circular dichroism, proteolytic studies, and other techniques that, in the absence of Pap1, Fip1 is largely, if not completely, unfolded. We speculate that flexibility may be important for Fip1's function as a molecular scaffold. Structure of yeast poly(A) polymerase in complex with a peptide from Fip1, an intrinsically disordered protein.,Meinke G, Ezeokonkwo C, Balbo P, Stafford W, Moore C, Bohm A Biochemistry. 2008 Jul 1;47(26):6859-69. Epub 2008 Jun 7. PMID:18537269[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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