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We are analyzing https://www.nature.com/articles/s41467-019-13906-8.

Title:
The proteasome 19S cap and its ubiquitin receptors provide a versatile recognition platform for substrates | Nature Communications
Description:
Proteins are targeted to the proteasome by the attachment of ubiquitin chains, which are markedly varied in structure. Three proteasome subunits–Rpn10, Rpn13, and Rpn1–can recognize ubiquitin chains. Here we report that proteins with single chains of K48-linked ubiquitin are targeted for degradation almost exclusively through binding to Rpn10. Rpn1 can act as a co-receptor with Rpn10 for K63 chains and for certain other chain types. Differences in targeting do not correlate with chain affinity to receptors. Surprisingly, in steady-state assays Rpn13 retarded degradation of various single-chain substrates. Substrates with multiple short ubiquitin chains can be presented for degradation by any of the known receptors, whereas those targeted to the proteasome through a ubiquitin-like domain are degraded most efficiently when bound by Rpn13 or Rpn1. Thus, the proteasome provides an unexpectedly versatile binding platform that can recognize substrates targeted for degradation by ubiquitin chains differing greatly in length and topology. Ubiquitylated proteins are degraded by the proteasome and the three proteasome subunits Rpn10, Rpn13 and Rpn1 recognize ubiquitin chains. Here the authors employ biochemical and kinetic assays and characterise the ubiquitin chain type specificities of these three ubiquitin receptors.
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Keywords {🔍}

ubiquitin, proteasome, chains, degradation, rpn, pubmed, substrate, article, proteins, substrates, google, scholar, cas, protein, klinked, fig, chain, supplementary, receptors, buffer, central, cell, degraded, binding, domain, biol, table, domains, min, receptor, proteasomes, nature, centrifugation, polyubiquitin, data, multiple, wildtype, fluorescence, ubkgfp, column, purified, trishcl, mol, dtt, cells, terminus, ubl, initial, site, function,

Topics {✒️}

nature portfolio privacy policy ubiquitin chain editing research design advertising suc-llvy-amc cleavage activity97 high-resolution cryo-em structure author information authors cdc48-rad23/dsk2 axis contributes social media important development apc/c-mediated multiple monoubiquitylation editing anti-flag immunoaffinity chromatography65 chromosome-coupled ubiquitin-proteasome pathway reprints incubated 50 µm suc‐llvy‐amc n-terminally 6xhis-tagged ubiquitin nature 453 nature 416 nature 532 nature 385 nature 5 mg ml−1 wild-type ubiquitin 25 mg ml−1 wild-type ubiquitin washed ni-nta beads n-terminal 6xhis-tag attached article martinez-fonts original author c-terminal flag-tag65 human anaphase-promoting complex single-molecule kinetic analysis pet duet-derived plasmids pgex-6p-1-derived plasmids substrates kirby martinez-fonts homotypic k11-linked chains34 15 µm ub-35-ub-gfp-tail room-temperature water bath peer review 80 µm e2 ube2s-ubd 60 µm e2 ube2s-ubd core-dependent activity element 4 mm dioxane-free iptg 5 mm dioxane-free iptg 2 mm dioxane-free iptg k48-linked diubiquitin complex ub/ubl-binding uim domain ensure single-turnover conditions ubiquitin-based tagging system 15 mg ml−1 flag peptide

Questions {❓}

  • Why do cellular proteins linked to K63-polyubiquitin chains not associate with proteasomes?
  • Why does the proteasome have multiple ubiquitin receptors?

Schema {🗺️}

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      description:Proteins are targeted to the proteasome by the attachment of ubiquitin chains, which are markedly varied in structure. Three proteasome subunits–Rpn10, Rpn13, and Rpn1–can recognize ubiquitin chains. Here we report that proteins with single chains of K48-linked ubiquitin are targeted for degradation almost exclusively through binding to Rpn10. Rpn1 can act as a co-receptor with Rpn10 for K63 chains and for certain other chain types. Differences in targeting do not correlate with chain affinity to receptors. Surprisingly, in steady-state assays Rpn13 retarded degradation of various single-chain substrates. Substrates with multiple short ubiquitin chains can be presented for degradation by any of the known receptors, whereas those targeted to the proteasome through a ubiquitin-like domain are degraded most efficiently when bound by Rpn13 or Rpn1. Thus, the proteasome provides an unexpectedly versatile binding platform that can recognize substrates targeted for degradation by ubiquitin chains differing greatly in length and topology. Ubiquitylated proteins are degraded by the proteasome and the three proteasome subunits Rpn10, Rpn13 and Rpn1 recognize ubiquitin chains. Here the authors employ biochemical and kinetic assays and characterise the ubiquitin chain type specificities of these three ubiquitin receptors.
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