Comprehensive picture of β-barrel transformation in the fibrillogenesis of odorant-binding proteins
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View abstract on PubMed
Summary
This summary is machine-generated.Odorant-binding proteins (OBPs) oligomerize before forming amyloid fibrils. Their β-barrel structure gradually weakens and reorganizes during fibrillogenesis, revealing potential inhibition targets.
Area Of Science
- Biochemistry
- Structural Biology
- Molecular Biology
Background
- Protein misfolding and fibrillogenesis can lead to cellular dysfunction.
- Odorant-binding proteins (OBPs) undergo fibrillogenesis initiated by C-terminal domain melting.
- Understanding the structural dynamics of OBPs during fibrillogenesis is crucial.
Purpose Of The Study
- To elucidate the sequence and duration of structural transformations in the OBP β-barrel during fibrillogenesis.
- To identify key intermediate states and molecular events preceding and during fibril formation.
Main Methods
- Investigated structural changes in OBPs during fibrillogenesis.
- Focused on the transformations within the β-barrel structure.
- Analyzed the role of oligomerization and C-terminal domain in fibril initiation.
Main Results
- OBP β-barrel transformation necessitates oligomerization of monomers with unlocked C-termini, preceding fibrillogenesis.
- The lag phase involves gradual β-barrel weakening, partial disruption of contacts near the β1-strand, and cavity opening.
- The exponential phase shows complete β-barrel reorganization into aggregates, including cytotoxic prefibrillar forms and mature amyloid fibrils.
Conclusions
- OBP fibrillogenesis involves a distinct sequence of structural transitions within the β-barrel.
- Similarities in intermediate states and mechanisms suggest common amyloidogenesis pathways for β-barrel proteins.
- Findings provide insights for identifying targets to inhibit amyloidogenesis in β-barrel proteins.
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