Extended β-Strands Contribute to Reversible Amyloid Formation

Area of Science:

• Biochemistry
• Structural Biology
• Molecular Biophysics

Background:

• Amyloid structures were historically viewed as irreversible and pathological.
• Recent research identifies reversible amyloid-like structures originating from protein low-complexity domains involved in cellular metabolism.

Purpose of the Study:

• To compare the atomic-level structures of reversible and irreversible amyloid fibrils.
• To identify structural features that distinguish reversible amyloid assembly.

Main Methods:

• Comparative analysis of atomic-level structures of amyloid fibrils.
• Quantum mechanical calculations to assess residue contributions to beta-sheet formation.

Main Results:

• Reversible fibrils exhibit a higher proportion of flattened beta-sheets compared to pleated ones.
• Flattened beta-sheets are formed by stacking extended beta-strands, favored by glycine residues.
• Intraresidue C5 hydrogen bonds stabilize extended beta-strands.
• Larger amino acid side chains promote shorter strands and pleated sheets.

Conclusions:

• Flattened beta-sheets, stabilized by specific amino acid properties like glycine, are a key structural determinant of reversible amyloid assembly.
• Understanding these structural elements can provide insights into the functional roles of reversible amyloids in cellular processes.