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TitleStructural Insights into Mdn1, an Essential AAA Protein Required for Ribosome Biogenesis.
Journal, issue, pagesCell, Vol. 175, Issue 3, Page 822-834.e18, Year 2018
Publish dateOct 18, 2018
AuthorsZhen Chen / Hiroshi Suzuki / Yuki Kobayashi / Ashley C Wang / Frank DiMaio / Shigehiro A Kawashima / Thomas Walz / Tarun M Kapoor /
PubMed AbstractMdn1 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 ...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.
External linksCell / PubMed:30318141 / PubMed Central
MethodsEM (single particle)
Resolution4.0 - 7.7 Å
Structure data

EMDB-9032, PDB-6or5:
Full-length S. pombe Mdn1 in the presence of AMPPNP (ring region)
Method: EM (single particle) / Resolution: 4.0 Å

EMDB-9033, PDB-6or6:
Full-length S. pombe Mdn1 in the presence of AMPPNP (tail region)
Method: EM (single particle) / Resolution: 4.6 Å

EMDB-9034:
C-terminally truncated S. pombe Mdn1 (1-3911 aa) in the presence of AMPPNP (ring region)
Method: EM (single particle) / Resolution: 6.1 Å

EMDB-9035:
C-terminally truncated S. pombe Mdn1 (1-3911 aa) in the presence of AMPPNP (tail region)
Method: EM (single particle) / Resolution: 7.4 Å

EMDB-9036, PDB-6orb:
Full-length S. pombe Mdn1 in the presence of ATP and Rbin-1
Method: EM (single particle) / Resolution: 7.2 Å

Chemicals

ChemComp-ANP:
PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER / AMP-PNP, energy-carrying molecule analogue*YM

Source
  • schizosaccharomyces pombe (fission yeast)
  • Schizosaccharomyces pombe (strain 972 / ATCC 24843) (yeast)
KeywordsMOTOR PROTEIN / Ribosome biogenesis / AAA protein / Mechanochemical enzyme / Ribosome assembly factor

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