Adapter-mediated substrate selection for endoplasmic reticulum-associated degradation

Kathleen Corcoran, Xiaoli Wang, Lonnie Lybarger

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

During endoplasmic reticulum (ER)-associated degradation (ERAD), a relatively small number of ubiquitin ligases (E3) must be capable of ubiquitinating an assortment of substrates diverse in both structure and location (ER lumen, membrane, and/or cytosol). Therefore, mechanisms that operate independently of primary sequence determinants must exist to ensure specificity during this process. Here we provide direct evidence for adapter-mediated substrate recruitment for a virus-encoded ERAD E3 ligase, mK3. Members of an ER membrane protein complex that normally functions during major histocompatibility complex class I biogenesis in the immune system are required for mK3 substrate selection. We demonstrate that heterologous substrates could be ubiquitinated by mK3 if they were recruited by these ER accessory molecules to the proper position relative to the ligase domain of mK3. This mechanism of substrate recruitment by adapter proteins may explain the ability of some E3 ligases, including cellular ERAD E3 ligases, to specifically target the ubiquitination of multiple substrates that are unrelated in sequence.

Original languageEnglish (US)
Pages (from-to)17475-17487
Number of pages13
JournalJournal of Biological Chemistry
Volume284
Issue number26
DOIs
StatePublished - Jun 26 2009

Fingerprint

Endoplasmic Reticulum-Associated Degradation
Ubiquitin-Protein Ligases
Endoplasmic Reticulum
Degradation
Substrates
Ubiquitination
Ligases
Major Histocompatibility Complex
Cytosol
Immune System
Membrane Proteins
Immune system
Accessories
Viruses
Membranes
Proteins
Molecules

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Adapter-mediated substrate selection for endoplasmic reticulum-associated degradation. / Corcoran, Kathleen; Wang, Xiaoli; Lybarger, Lonnie.

In: Journal of Biological Chemistry, Vol. 284, No. 26, 26.06.2009, p. 17475-17487.

Research output: Contribution to journalArticle

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