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An Extended Conformation for K48 Ubiquitin Chains Revealed by the hRpn2:Rpn13:K48-Diubiquitin Structure

  1. Author:
    Lu,Xiuxiu
    Ebelle, Danielle L
    Matsuo,Hiroshi
    Walters,Kylie

  2. Author Address

    Protein Processing Section, Structural Biophysics Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA., Basic Research Laboratory, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA., Protein Processing Section, Structural Biophysics Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. Electronic address: kylie.walters@nih.gov.,
    1. Year: 2020
    2. Date: May 5
    3. Epub Date: 2020 03 09
  2. Journal: Structure (London, England : 1993)
    1. 28
    2. 5
    3. Pages: 495-506.e3
  4. Type of Article: Article
  5. ISSN: 0969-2126
  1. Abstract:

    Rpn13/Adrm1 is recruited to the proteasome by PSMD1/Rpn2, where it serves as a substrate receptor that binds preferentially to K48-linked ubiquitin chains, an established signal for protein proteolysis. Here, we use NMR to solve the structure of hRpn13 Pru:hRpn2 (940-953):K48-diubiquitin. Surprisingly, hRpn2-bound hRpn13 selects a dynamic, extended conformation of K48-diubiquitin that is unique from previously determined structures. NMR experiments on free K48-diubiquitin demonstrate the presence of the reported "closed" conformation observed by crystallography, but also this more extended state, in which the hRpn13-binding surface is exposed. This extended K48-diubiquitin conformation is defined by interactions between L73 from G76-linked (distal) ubiquitin and a Y59-centered surface of K48-linked (proximal) ubiquitin. Furthermore, hRpn13 exchanges between the two ubiquitins within 100 ms, although prefers the proximal ubiquitin due to interactions with the K48 linker region. Altogether, these data lead to a revised model of how ubiquitinated substrates interact with the proteasome. Published by Elsevier Ltd.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.str.2020.02.007
  3. PMID: 32160516
  4. View record in Web of Science®
  5. WOS: 000531055000003
  6. PII : S0969-2126(20)30071-X

Library Notes

  1. Fiscal Year: FY2019-2020
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