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Cryo-EM Reveals Active Site Coordination Within a Multienzyme pre-rRNA Processing Complex

Ribosome assembly is a complex process reliant on the coordination of trans-acting enzymes to produce functional ribosomal subunits and secure the translational capacity of cells. The endoribonuclease (RNase) Las1 and the poly-nucleotide kinase (PNK) Grc3 assemble into a multienzyme complex, herein...

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Detalles Bibliográficos
Autores principales: Pillon, Monica C., Hsu, Allen L., Krahn, Juno M., Williams, Jason G., Goslen, Kevin H., Sobhany, Mack, Borgnia, Mario J., Stanley, Robin E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733591/
https://www.ncbi.nlm.nih.gov/pubmed/31488907
http://dx.doi.org/10.1038/s41594-019-0289-8
Descripción
Sumario:Ribosome assembly is a complex process reliant on the coordination of trans-acting enzymes to produce functional ribosomal subunits and secure the translational capacity of cells. The endoribonuclease (RNase) Las1 and the poly-nucleotide kinase (PNK) Grc3 assemble into a multienzyme complex, herein designated RNase PNK, to orchestrate processing of precursor ribosomal RNA. RNase PNK belongs to the functionally-diverse HEPN nuclease superfamily, whose members rely on distinct cues for nuclease activation. To establish how RNase PNK coordinates its dual enzymatic activities, we solved a series of cryo-electron microscopy structures of Chaetomium thermophilum RNase PNK in multiple conformational states. The structures reveal that RNase PNK adopts a butterfly-like architecture harboring a composite HEPN nuclease active site flanked by discrete RNA kinase sites. We identify two molecular switches that coordinate nuclease and kinase function. Together our structures and corresponding functional studies establish a new mechanism of HEPN nuclease activation essential for ribosome production.