Inclusion bodies: specificity in their aggregation process and amyloid-like structure

Area of Science:

• Biochemistry
• Molecular Biology
• Cell Biology

Background:

• Protein aggregation is linked to disease pathology and challenges in protein production.
• Intracellular aggregates were traditionally considered nonspecific, but in vitro studies suggest specific interactions.
• The specificity of in vivo protein deposition remains poorly understood.

Purpose of the Study:

• To investigate the in vivo co-aggregation specificity between amyloid-beta 42 (Abeta42) and foot-and-mouth disease virus VP1 capsid protein in prokaryotic cells.
• To explore the ultrastructure of intracellular aggregates and compare it with amyloid fibrils.
• To determine if conserved mechanisms underlie protein aggregation across different organisms.

Main Methods:

• Co-expression of Abeta42 and VP1 in prokaryotic cells.
• Analysis of in vivo protein aggregation using electron microscopy.
• Assessment of the seeding potential of intracellular aggregates for Abeta42 amyloid fibril formation.

Main Results:

• In vivo protein aggregation demonstrates remarkable specificity through selective interactions.
• Intracellular aggregates form oligomeric and fibrillar structures with amyloid-like properties.
• Prokaryotic Abeta42 intracellular aggregates effectively seed the formation of Abeta42 amyloid fibrils.

Conclusions:

• Conserved mechanisms govern protein aggregation in diverse organisms.
• In vivo protein aggregation is a specific process with implications for biotechnology and medicine.
• Understanding specific aggregation pathways is crucial for addressing protein misfolding diseases and improving recombinant protein production.