Extended β-Strands Contribute to Reversible Amyloid Formation

The assembly of proteins into fibrillar amyloid structures was once considered to be pathologic and essentially irreversible. Recent studies reveal amyloid-like structures that form reversibly, derived from protein low-complexity domains which function in cellular metabolism. Here, by comparing atomic-level structures of reversible and irreversible amyloid fibrils, we find that the beta-sheets of reversible fibrils are enriched in flattened (as opposed to pleated) beta-sheets formed by stacking of extended beta-strands. Quantum mechanical calculations show that glycine residues favor extended beta-strands which may be stabilized by intraresidue interactions between the amide proton and the carbonyl oxygen, known as C5 hydrogen-bonds. Larger residue side chains favor shorter strands and pleated sheets. These findings highlight a structural element that may regulate reversible amyloid assembly.

Automated summary

Recent studies have revealed that some amyloid-like structures are reversible and derived from protein low-complexity domains involved in cellular metabolism. The finding of unique structural features of reversible amyloid fibrils suggests the involvement of intraresidue interactions known as C5 hydrogen-bonds in stabilizing these structures.