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@ARTICLE{Shiber:137657,
      author       = {A. Shiber$^*$ and K. Döring$^*$ and U. A. Friedrich$^*$
                      and K. Klann$^*$ and D. Merker$^*$ and M. M. A. Zedan$^*$
                      and F. Tippmann$^*$ and G. Kramer$^*$ and B. Bukau$^*$},
      title        = {{C}otranslational assembly of protein complexes in
                      eukaryotes revealed by ribosome profiling.},
      journal      = {Nature},
      volume       = {561},
      number       = {7722},
      issn         = {1476-4687},
      address      = {London [u.a.]},
      publisher    = {Nature Publ. Group},
      reportid     = {DKFZ-2018-01536},
      pages        = {268 - 272},
      year         = {2018},
      note         = {DKFZ-ZMBH-Allianz},
      abstract     = {The folding of newly synthesized proteins to the native
                      state is a major challenge within the crowded cellular
                      environment, as non-productive interactions can lead to
                      misfolding, aggregation and degradation1. Cells cope with
                      this challenge by coupling synthesis with polypeptide
                      folding and by using molecular chaperones to safeguard
                      folding cotranslationally2. However, although most of the
                      cellular proteome forms oligomeric assemblies3, little is
                      known about the final step of folding: the assembly of
                      polypeptides into complexes. In prokaryotes, a
                      proof-of-concept study showed that the assembly of
                      heterodimeric luciferase is an organized cotranslational
                      process that is facilitated by spatially confined
                      translation of the subunits encoded on a polycistronic
                      mRNA4. In eukaryotes, however, fundamental differences-such
                      as the rarity of polycistronic mRNAs and different chaperone
                      constellations-raise the question of whether assembly is
                      also coordinated with translation. Here we provide a
                      systematic and mechanistic analysis of the assembly of
                      protein complexes in eukaryotes using ribosome profiling. We
                      determined the in vivo interactions of the nascent subunits
                      from twelve hetero-oligomeric protein complexes of
                      Saccharomyces cerevisiae at near-residue resolution. We find
                      nine complexes assemble cotranslationally; the three
                      complexes that do not show cotranslational interactions are
                      regulated by dedicated assembly chaperones5-7.
                      Cotranslational assembly often occurs uni-directionally,
                      with one fully synthesized subunit engaging its nascent
                      partner subunit, thereby counteracting its propensity for
                      aggregation. The onset of cotranslational subunit
                      association coincides directly with the full exposure of the
                      nascent interaction domain at the ribosomal tunnel exit. The
                      action of the ribosome-associated Hsp70 chaperone Ssb8 is
                      coordinated with assembly. Ssb transiently engages partially
                      synthesized interaction domains and then dissociates before
                      the onset of partner subunit association, presumably to
                      prevent premature assembly interactions. Our study shows
                      that cotranslational subunit association is a prevalent
                      mechanism for the assembly of hetero-oligomers in yeast and
                      indicates that translation, folding and the assembly of
                      protein complexes are integrated processes in eukaryotes.},
      cin          = {A250},
      ddc          = {500},
      cid          = {I:(DE-He78)A250-20160331},
      pnm          = {321 - Basic Concepts (POF3-321)},
      pid          = {G:(DE-HGF)POF3-321},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:30158700},
      doi          = {10.1038/s41586-018-0462-y},
      url          = {https://inrepo02.dkfz.de/record/137657},
}