Crystal structure of mammalian poly(A) polymerase in complex with an analog of ATP

AUTOR(ES)

Martin, Georges

FONTE

Oxford University Press

RESUMO

In eukaryotes, polyadenylation of pre-mRNA plays an essential role in the initiation step of protein synthesis, as well as in the export and stability of mRNAs. Poly(A) polymerase, the enzyme at the heart of the polyadenylation machinery, is a template-independent RNA polymerase which specifically incorporates ATP at the 3′ end of mRNA. We have solved the crystal structure of bovine poly(A) polymerase bound to an ATP analog at 2.5 Å resolution. The structure revealed expected and unexpected similarities to other proteins. As expected, the catalytic domain of poly(A) polymerase shares substantial structural homology with other nucleotidyl transferases such as DNA polymerase β and kanamycin transferase. The C-terminal domain unexpectedly folds into a compact domain reminiscent of the RNA-recognition motif fold. The three invariant aspartates of the catalytic triad ligate two of the three active site metals. One of these metals also contacts the adenine ring. Furthermore, conserved, catalytically important residues contact the nucleotide. These contacts, taken together with metal coordination of the adenine base, provide a structural basis for ATP selection by poly(A) polymerase.

Documentos Relacionados

• Complex alternative RNA processing generates an unexpected diversity of poly(A) polymerase isoforms.
• Poly(A) Polymerase Activity in Reovirus
• Poly(A) Polymerase and Poly(G) Polymerase in Wheat Chloroplasts
• Isolation and expression of cDNA clones encoding mammalian poly(A) polymerase.
• Deregulation of Poly(A) Polymerase Interferes with Cell Growth