Skip NavigationSkip to Content
Return Return to Search Results

E6AP AZUL interaction with UBQLN1/2 in cells, condensates, and an AlphaFold-NMR integrated structure

  1. Author:
    Buel,Gwen
    Chen,Xiang
    Myint,Wazo
    Kayode, Olumide
    Folimonova,Varvara
    Cruz, Anthony
    Skorupka,Kate
    Matsuo,Hiroshi
    Walters,Kylie

  2. Author Address

    Protein Processing Section, Center for Structural Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA., Cancer Innovation Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA., Protein Processing Section, Center for Structural Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA. Electronic address: kylie.walters@nih.gov.,
    1. Year: 2023
    2. Date: Feb 14
    3. Epub Date: 2023 02 14
  2. Journal: Structure (London, England : 1993)
    1. 31
    2. 4
    3. Pages: 395-410
  4. Type of Article: Article
  1. Abstract:

    The E3 ligase E6AP/UBE3A has a dedicated binding site in the 26S proteasome provided by the RAZUL domain of substrate receptor hRpn10/S5a/PSMD4. Guided by RAZUL sequence similarity, we test and demonstrate here that the E6AP AZUL binds transiently to the UBA of proteasomal shuttle factor UBQLN1/2. Despite a weak binding affinity, E6AP AZUL is recruited to UBQLN2 biomolecular condensates in vitro and E6AP interacts with UBQLN1/2 in cellulo. Steady-state and transfer nuclear Overhauser effect (NOE) experiments indicate direct interaction of AZUL with UBQLN1 UBA. Intermolecular contacts identified by NOE spectroscopy (NOESY) data were combined with AlphaFold2-Multimer predictions to yield an AZUL:UBA model structure. We additionally identify an oligomerization domain directly adjacent to UBQLN1/2 UBA (UBA adjacent [UBAA]) that is a-helical and allosterically reconfigured by AZUL binding to UBA. These data lead to a model of E6AP recruitment to UBQLN1/2 by AZUL:UBA interaction and provide fundamental information on binding requirements for interactions in condensates and cells. Published by Elsevier Ltd.

    See More

  1. Keywords:

External Sources

  1. View Full Text
  2. DOI: 10.1016/j.str.2023.01.012
  3. PMID: 36827983
  4. PII : S0969-2126(23)00033-3

Library Notes

  1. Fiscal Year: FY2022-2023
NCI at Frederick

You are leaving a government website.

This external link provides additional information that is consistent with the intended purpose of this site. The government cannot attest to the accuracy of a non-federal site.

Linking to a non-federal site does not constitute an endorsement by this institution or any of its employees of the sponsors or the information and products presented on the site. You will be subject to the destination site's privacy policy when you follow the link.

ContinueCancel