Amyloid fibril formation by a helical cytochrome

Abstract
The substitution of alanines for the two cysteines which form thioether linkages to the haem group in cytochrome c 552 from Hydogenobacter thermophilus destabilises the native protein fold. The holo form of this variant slowly converts into a partially folded apo state that over prolonged periods of time aggregates into fibrillar structures. Characterisation of these structures by electron microscopy and thioflavin‐T binding assays shows that they are amyloid fibrils. The data demonstrate that when the native state of this cytochrome is destabilised by loss of haem, even this highly α‐helical protein can form β‐sheet structures of the type most commonly associated with protein deposition diseases.