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Published on: September 30, 2011

Dynamic interactions of Sup35p and PrP prion protein domains modulate aggregate nucleation and seeding

Carmen Krammer1, Elisabeth Kremmer, Hermann M Schätzl

  • 1Institute of Virology, Technische Universität München, Munich, Germany.

Prion
|February 7, 2009
PubMed

Insights

Prion formation mechanisms remain unclear. This study reveals that protein sequence similarity is crucial for cross-seeding, influencing prion aggregate nucleation and formation dynamics.

Area of Science:

  • Neuroscience
  • Biochemistry
  • Molecular Biology

Background:

  • Prions are infectious proteins causing neurodegenerative diseases.
  • The precise mechanisms of prion formation and propagation are not fully understood.
  • Investigating prion aggregation in cellular models is key to understanding these mechanisms.

Purpose of the Study:

  • To investigate the aggregation propensities of chimeric prion proteins.
  • To explore the role of specific protein domains in prion formation.
  • To determine the requirements for cross-seeding between different prion proteins.

Main Methods:

  • Comparative analysis of chimeric proteins derived from yeast Sup35p and mouse PrP in neuroblastoma cells.
  • Cytosolic expression of Sup35p domains (NM) and PrP domains.
  • Co-aggregation studies using chimeric proteins, cytosolic PrP, and huntingtin fragments.

Main Results:

  • The carboxy-terminal domain of mouse PrP (PrP90-230) mediated aggregate formation.
  • Yeast Sup35p N and M domains modulated aggregate size and frequency when fused to PrP.
  • Cross-seeding between heterologous proteins necessitates sequence similarity within the aggregated domain.

Conclusions:

  • Prion aggregate nucleation and seeding are significantly influenced by interactions between the core-forming domain and flanking regions.
  • Sequence similarity is a critical factor for cross-seeding events between different prion proteins.
  • Understanding these domain interactions provides insights into prion disease mechanisms.

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