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Rpn1 provides adjacent receptor sites for substrate binding and deubiquitination by the proteasome

Yuan Shi1, Xiang Chen2, Suzanne Elsasser1

  • 1Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.

Science (New York, N.Y.)
|February 26, 2016
PubMed

Insights

Researchers identified a sixth proteasomal ubiquitin receptor, Rpn1, in yeast. Rpn1 has two binding sites that recognize ubiquitin and ubiquitin-like domains, crucial for protein degradation pathways.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Background:

  • Protein degradation is essential for cellular function.
  • The proteasome is a key cellular machine responsible for protein degradation.
  • Ubiquitin recognition is a critical step in targeting proteins for proteasomal degradation.

Purpose of the Study:

  • To identify novel ubiquitin receptors for the proteasome.
  • To elucidate the mechanism of ubiquitin recognition by the proteasome.
  • To understand the role of Rpn1 in substrate selection and processing.

Main Methods:

  • Yeast genetics and biochemistry
  • Proteasome purification and analysis
  • X-ray crystallography of Rpn1-ubiquitin complexes

Main Results:

  • The five known proteasomal ubiquitin receptors are not essential for ubiquitin recognition in yeast.
  • A sixth receptor, Rpn1, was identified and characterized.
  • Rpn1 possesses two distinct binding sites (T1 and T2) for ubiquitin and ubiquitin-like (UBL) domains.
  • The T1 site preferentially binds lysine 48-linked ubiquitin chains, mediating substrate recognition.
  • The T2 site binds the UBL domain of deubiquitinating enzyme Ubp6, facilitating ubiquitin chain disassembly.

Conclusions:

  • Rpn1 is a novel and essential proteasomal ubiquitin receptor in yeast.
  • The dual-site recognition mechanism of Rpn1 is critical for efficient protein degradation.
  • Rpn1 integrates substrate recognition, shuttling factor interaction, and deubiquitination for proteasomal processing.

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