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Updated: Aug 5, 2026
06:33
Genetic Analysis of Hereditary Transthyretin Ala97Ser Related Amyloidosis
Published on: June 9, 2018
From Hummingbird to Elephant: Amyloid Formation in Natural Transthyretin Variants
Biorxiv : the Preprint Server for Biology
|July 29, 2026
Summary
Mechanical agitation reveals distinct Transthyretin (TTR) aggregation patterns in hummingbirds and elephants compared to humans. These differences in TTR protein misfolding offer evolutionary insights.
Area of Science:
- Biochemistry
- Protein Misfolding
- Evolutionary Biology
Background:
- Transthyretin (TTR) is implicated in cardiac and other amyloid diseases due to protein misfolding.
- Previous studies demonstrated TTR aggregation and fibril formation upon agitation of human TTR solutions at neutral pH.
Purpose of the Study:
- To investigate the aggregation behavior of TTR from species with diverse heart rates (Anna's hummingbird and African elephant) when subjected to mechanical agitation.
- To compare the aggregation characteristics of avian (hbTTR) and elephantine (aeTTR) TTR with human TTR (huTTR).
Main Methods:
- Mechanical agitation of TTR solutions from different species (hummingbird, elephant, human) at neutral pH.
- Characterization of aggregates using mass photometry and electron microscopy.
- Assessment of protein denaturation resistance using 8 M urea.
Main Results:
- Agitation-induced TTR aggregation varied significantly across species.
- Anna's hummingbird TTR (hbTTR) exhibited slow aggregation, forming smaller, fibrillar aggregates and showing resistance to urea denaturation.
- African elephant TTR (aeTTR) displayed rapid aggregation, favoring larger, amorphous particles.
- Spherical, early-stage oligomeric intermediates were observed in all TTR variants.
Conclusions:
- Naturally occurring TTR variants display distinct aggregation behaviors in response to mechanical stress under near-physiological conditions.
- Small sequence variations in TTR can influence protein aggregation and potentially contribute to evolutionary fitness.
- Understanding species-specific TTR aggregation provides insights into disease mechanisms and evolutionary adaptations.
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