Premium
Amyloid fibril formation by a helical cytochrome
Author(s) -
Pertinhez Thelma A.,
Bouchard Mario,
Tomlinson Esther J.,
Wain Rachel,
Ferguson Stuart J.,
Dobson Christopher M.,
Smith Lorna J.
Publication year - 2001
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(01)02384-5
Subject(s) - thioflavin , thioether , cytochrome , cytochrome c , chemistry , amyloid (mycology) , fibril , hemeprotein , protein structure , protein folding , crystallography , electron microscope , biophysics , protein aggregation , biochemistry , stereochemistry , heme , mitochondrion , biology , enzyme , alzheimer's disease , medicine , inorganic chemistry , physics , disease , pathology , optics
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.