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Cell. 2018 Oct 18;175(3):822-834.e18. doi: 10.1016/j.cell.2018.09.015. Epub 2018 Oct 11.

Structural Insights into Mdn1, an Essential AAA Protein Required for Ribosome Biogenesis.

Author information

1
Laboratory of Chemistry and Cell Biology, The Rockefeller University, New York, NY 10065, USA.
2
Laboratory of Molecular Electron Microscopy, The Rockefeller University, New York, NY 10065, USA.
3
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 1130033, Japan.
4
Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
5
Laboratory of Molecular Electron Microscopy, The Rockefeller University, New York, NY 10065, USA. Electronic address: twalz@rockefeller.edu.
6
Laboratory of Chemistry and Cell Biology, The Rockefeller University, New York, NY 10065, USA. Electronic address: kapoor@rockefeller.edu.

Abstract

Mdn1 is an essential AAA (ATPase associated with various activities) protein that removes assembly factors from distinct precursors of the ribosomal 60S subunit. However, Mdn1's large size (∼5,000 amino acid [aa]) and its limited homology to other well-studied proteins have restricted our understanding of its remodeling function. Here, we present structures for S. pombe Mdn1 in the presence of AMPPNP at up to ∼4 Å or ATP plus Rbin-1, a chemical inhibitor, at ∼8 Å resolution. These data reveal that Mdn1's MIDAS domain is tethered to its ring-shaped AAA domain through an ∼20 nm long structured linker and a flexible ∼500 aa Asp/Glu-rich motif. We find that the MIDAS domain, which also binds other ribosome-assembly factors, docks onto the AAA ring in a nucleotide state-specific manner. Together, our findings reveal how conformational changes in the AAA ring can be directly transmitted to the MIDAS domain and thereby drive the targeted release of assembly factors from ribosomal 60S-subunit precursors.

KEYWORDS:

60S subunit; AAA protein; MIDAS domain; chemical inhibitor; dynein-like protein; midasin; ribosome biogenesis; ribozinoindole; single-particle cryo-EM structure

PMID:
30318141
PMCID:
PMC6289053
[Available on 2019-10-18]
DOI:
10.1016/j.cell.2018.09.015

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