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Single Amino Acid-Based Control of Fibril Supramolecular Chirality.
Jadon Sitton1, Dmitry Kurouski1,2
1Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843, United States.
The Journal of Physical Chemistry Letters
|June 2, 2026
Summary
Supramolecular chirality in biological molecules like amyloid fibrils is key to their function. We found that a single amino acid and its protonation state can control this chirality, impacting aggregate self-assembly.
Area of Science:
- Biochemistry and structural biology
- Molecular self-assembly
- Chirality in biological systems
Background:
- Supramolecular chirality dictates the physiological roles of biological macromolecules.
- The factors governing the supramolecular organization of macromolecules are not well understood.
- Amyloid fibrils are a key class of biological macromolecules where supramolecular organization is critical.
Purpose of the Study:
- To investigate the factors controlling supramolecular chirality in amyloid fibrils.
- To understand the role of individual amino acids in amyloid fibril self-assembly.
- To elucidate the mechanism of functional and pathological amyloid aggregate formation.
Main Methods:
- Investigated the impact of single amino acid variations on amyloid fibril structure.
- Analyzed the effect of amino acid protonation state on supramolecular chirality.
- Utilized biophysical techniques to characterize amyloid fibril self-assembly.
Main Results:
- Demonstrated that a single amino acid can determine the supramolecular chirality of amyloid fibrils.
- Showed that the protonation state of an amino acid is a critical factor in controlling supramolecular chirality.
- Identified specific amino acid properties that influence amyloid fibril organization.
Conclusions:
- Supramolecular chirality of amyloid fibrils is controllable.
- Single amino acids and their protonation states are key determinants of amyloid fibril supramolecular organization.
- Findings provide crucial insights into the self-assembly mechanisms of functional and pathological amyloid aggregates.
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