title: The structure of the Pan2-Pan3 core complex reveals cross-talk between deadenylase and pseudokinase.
abstract: Pan2-Pan3 is a conserved complex involved in the shortening of mRNA poly(A) tails, the initial step in eukaryotic mRNA turnover. We show that recombinant Saccharomyces cerevisiae Pan2-Pan3 can deadenylate RNAs in vitro without needing the poly(A)-binding protein Pab1. The crystal structure of an active ~200-kDa core complex reveals that Pan2 and Pan3 interact with an unusual 1:2 stoichiometry imparted by the asymmetric nature of the Pan3 homodimer. An extended region of Pan2 wraps around Pan3 and provides a major anchoring point for complex assembly. A Pan2 module formed by the pseudoubiquitin-hydrolase and RNase domains latches onto the Pan3 pseudokinase with intertwined interactions that orient the deadenylase active site toward the A-binding site of the interacting Pan3. The molecular architecture of Pan2-Pan3 suggests how the nuclease and its pseudokinase regulator act in synergy to promote deadenylation.
authors.affiliation: Structural Cell Biology Department, Max Planck Institute of Biochemistry, Martinsried, Germany.
authors.forename: Ingmar B
authors.initials: IB
authors.lastname: Schäfer
authors.affiliation: Structural Cell Biology Department, Max Planck Institute of Biochemistry, Martinsried, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Rode
authors.affiliation: Structural Cell Biology Department, Max Planck Institute of Biochemistry, Martinsried, Germany.
authors.forename: Fabien
authors.initials: F
authors.lastname: Bonneau
authors.affiliation: Structural Cell Biology Department, Max Planck Institute of Biochemistry, Martinsried, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Schüssler
authors.affiliation: Structural Cell Biology Department, Max Planck Institute of Biochemistry, Martinsried, Germany.
authors.forename: Elena
authors.initials: E
authors.lastname: Conti
mesh_terms: D001665:Binding Sites; D018360:Crystallography, X-Ray; D005095:Exoribonucleases / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D008954:Models, Biological; D039102:Poly(A)-Binding Proteins / Q000502:physiology; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology
chemical_list: D005095:Exoribonucleases; D039102:Poly(A)-Binding Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; C450100:pab1 protein, S cerevisiae; C101747:PAN3 protein, S cerevisiae