Structural basis for the antagonistic roles of RNP-8 and GLD-3 in GLD-2 poly(A)-polymerase activity.
Cytoplasmic polyadenylation drives the translational activation of specific mRNAs in early metazoan development and is performed by distinct complexes that share the same catalytic poly(A)-polymerase subunit, GLD-2. The activity and specificity of GLD-2 depend on its binding partners. In Caenorhabditis elegans, GLD-2 promotes spermatogenesis when bound to GLD-3 and oogenesis when bound to RNP-8. GLD-3 and RNP-8 antagonize each other and compete for GLD-2 binding. Following up on our previous mechanistic studies of GLD-2-GLD-3, we report here the 2.5 Å resolution structure and biochemical characterization of a GLD-2-RNP-8 core complex. In the structure, RNP-8 embraces the poly(A)-polymerase, docking onto several conserved hydrophobic hotspots present on the GLD-2 surface. RNP-8 stabilizes GLD-2 and indirectly stimulates polyadenylation. RNP-8 has a different amino-acid sequence and structure as compared to GLD-3. Yet, it binds the same surfaces of GLD-2 by forming alternative interactions, rationalizing the remarkable versatility of GLD-2 complexes.
Department of Structural Cell Biology, Max-Planck-Institute of Biochemistry, D-82152 Martinsried, Germany.
Katharina
K
Nakel
Department of Structural Cell Biology, Max-Planck-Institute of Biochemistry, D-82152 Martinsried, Germany.
Fabien
F
Bonneau
Department of Structural Cell Biology, Max-Planck-Institute of Biochemistry, D-82152 Martinsried, Germany.
Claire
C
Basquin
Department of Structural Cell Biology, Max-Planck-Institute of Biochemistry, D-82152 Martinsried, Germany.
Bianca
B
Habermann
Department of Genetics, Martin-Luther-University of Halle-Wittenberg, Institute of Biology, 06120 Halle (Saale), Germany.
Christian R
CR
Eckmann
Department of Structural Cell Biology, Max-Planck-Institute of Biochemistry, D-82152 Martinsried, Germany.
Elena
E
Conti
D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry* / Q000502:physiology; D018360:Crystallography, X-Ray; D011062:Polynucleotide Adenylyltransferase / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D011487:Protein Conformation; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000502:physiology; D012261:Ribonucleoproteins / Q000737:chemistry* / Q000502:physiology
D029742:Caenorhabditis elegans Proteins; C469731:GLD-3 protein, C elegans; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; C491056:GLD-2 protein, C elegans; D011062:Polynucleotide Adenylyltransferase
C. elegans; cytoplasmic polyadenylation; germline development; nucleotidyl-transferase; translational regulation