Structural basis of GTPase-mediated mitochondrial ribosome biogenesis and recycling

2021-06-16 | journal article; research paper. A publication with affiliation to the University of Göttingen.

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​Structural basis of GTPase-mediated mitochondrial ribosome biogenesis and recycling​
Hillen, H. S.; Lavdovskaia, E.; Nadler, F.; Hanitsch, E.; Linden, A.; Bohnsack, K. E. & Urlaub, H. et al.​ (2021) 
Nature Communications12(1) art. 3672​.​ DOI: https://doi.org/10.1038/s41467-021-23702-y 

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Authors
Hillen, Hauke S.; Lavdovskaia, Elena; Nadler, Franziska; Hanitsch, Elisa; Linden, Andreas; Bohnsack, Katherine E.; Urlaub, Henning; Richter-Dennerlein, Ricarda 
Abstract
Abstract Ribosome biogenesis requires auxiliary factors to promote folding and assembly of ribosomal proteins and RNA. Particularly, maturation of the peptidyl transferase center (PTC) is mediated by conserved GTPases, but the molecular basis is poorly understood. Here, we define the mechanism of GTPase-driven maturation of the human mitochondrial large ribosomal subunit (mtLSU) using endogenous complex purification, in vitro reconstitution and cryo-EM. Structures of transient native mtLSU assembly intermediates that accumulate in GTPBP6-deficient cells reveal how the biogenesis factors GTPBP5, MTERF4 and NSUN4 facilitate PTC folding. Addition of recombinant GTPBP6 reconstitutes late mtLSU biogenesis in vitro and shows that GTPBP6 triggers a molecular switch and progression to a near-mature PTC state. Additionally, cryo-EM analysis of GTPBP6-treated mature mitochondrial ribosomes reveals the structural basis for the dual-role of GTPBP6 in ribosome biogenesis and recycling. Together, these results provide a framework for understanding step-wise PTC folding as a critical conserved quality control checkpoint.
Maturation of the ribosomal peptidyl transferase center (PTC) is mediated by universally conserved GTPases. Here, cryo-EM structures of mitochondrial ribosomal large subunit assembly intermediates and of mature ribosomes offer insight into the roles of several assembly factors, including GTPBP6’s role in both ribosome biogenesis and recycling.
Issue Date
16-June-2021
Journal
Nature Communications 
Project
EXC 2067: Multiscale Bioimaging 
Working Group
RG Hillen (Structure and Function of Molecular Machines) 
RG Richter-Dennerlein (Mitoribosome Assembly) 
External URL
https://mbexc.uni-goettingen.de/literature/publications/316
eISSN
2041-1723
Language
English
Sponsor
Deutsche Forschungsgemeinschaft (German Research Foundation) https://doi.org/10.13039/501100001659
Max-Planck-Gesellschaft (Max Planck Society) https://doi.org/10.13039/501100004189

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