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Structure. 2012 Dec 5;20(12):2138-50. doi: 10.1016/j.str.2012.09.020. Epub 2012 Nov 1.

Promiscuous interactions of gp78 E3 ligase CUE domain with polyubiquitin chains.

Author information

  • 1Structural Biophysics Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702-1201, USA.

Abstract

Recognition of ubiquitin and polyubiquitin chains by ubiquitin-binding domains (UBDs) is vital for ubiquitin-mediated signaling pathways. The endoplasmic reticulum resident RING finger ubiquitin ligase (E3) gp78 regulates critical proteins via the ubiquitin-proteasome system to maintain cellular homeostasis and includes a UBD known as the CUE domain, which is essential for function. A probable role of this domain is to recognize ubiquitin-modified substrates, enabling gp78 to assemble polyubiquitin chains on these substrates and mark them for degradation. Here, we report the molecular details of the interaction of gp78CUE domain with ubiquitin and diubiquitin. The gp78CUE domain exhibits a well-defined set of interactions with ubiquitin and a dynamic, promiscuous interaction with diubiquitin chains. This leads to a model in which the CUE domain functions to both facilitate substrate binding and enable switching between adjacent ubiquitin molecules of a growing chain to enable processivity in ubiquitination.

Copyright © 2012 Elsevier Ltd. All rights reserved.

PMID:
23123110
[PubMed - indexed for MEDLINE]
PMCID:
PMC3518592
Free PMC Article

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