Structure of the active form of Dcp1-Dcp2 decapping enzyme bound to m7GDP and its Edc3 activator.
Elimination of the 5' cap of eukaryotic mRNAs, known as decapping, is considered to be a crucial, irreversible and highly regulated step required for the rapid degradation of mRNA by Xrn1, the major cytoplasmic 5'-3' exonuclease. Decapping is accomplished by the recruitment of a protein complex formed by the Dcp2 catalytic subunit and its Dcp1 cofactor. However, this complex has a low intrinsic enzymatic activity and requires several accessory proteins such as the Lsm1-7 complex, Pat1, Edc1-Edc2 and/or Edc3 to be fully active. Here we present the crystal structure of the active form of the yeast Kluyveromyces lactis Dcp1-Dcp2 enzyme bound to its product (m7GDP) and its potent activator Edc3. This structure of the Dcp1-Dcp2 complex bound to a cap analog further explains previously published data on substrate binding and provides hints as to the mechanism of Edc3-mediated Dcp2 activation.
Laboratoire de Biochimie, Ecole Polytechnique, CNRS, Université Paris-Saclay, Palaiseau, France.
Clément
C
Charenton
Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France.|Centre National de Recherche Scientifique (CNRS) UMR 7104, Illkirch, France.|Institut National de Santé et de Recherche Médicale (INSERM) U964, Illkirch, France.|Université de Strasbourg, Illkirch, France.
Valerio
V
Taverniti
Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France.|Centre National de Recherche Scientifique (CNRS) UMR 7104, Illkirch, France.|Institut National de Santé et de Recherche Médicale (INSERM) U964, Illkirch, France.|Université de Strasbourg, Illkirch, France.
Claudine
C
Gaudon-Plesse
Laboratoire de Biochimie, Ecole Polytechnique, CNRS, Université Paris-Saclay, Palaiseau, France.
Régis
R
Back
Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France.|Centre National de Recherche Scientifique (CNRS) UMR 7104, Illkirch, France.|Institut National de Santé et de Recherche Médicale (INSERM) U964, Illkirch, France.|Université de Strasbourg, Illkirch, France.
Bertrand
http://orcid.org/0000-0002-5168-1921
B
Séraphin
Laboratoire de Biochimie, Ecole Polytechnique, CNRS, Université Paris-Saclay, Palaiseau, France.
Marc
M
Graille
D018360:Crystallography, X-Ray; D004722:Endoribonucleases / Q000737:chemistry / Q000378:metabolism*; D004789:Enzyme Activation; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism*; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives* / Q000378:metabolism; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D020871:RNA Stability; D004718:Saccharomycetales / Q000737:chemistry / Q000378:metabolism*
D005656:Fungal Proteins; C030052:mRNA decapping enzymes; C111106:7-methylguanosine 5'-diphosphate; D006153:Guanosine Diphosphate; D004722:Endoribonucleases
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