On the molecular mechanism of amyloid fibrillogenesis

Abstract

Amyloid fibrils are known to form out of partially unfolded human lysozyme through self‐assembly of its disordered sequences into a cross‐β structure. A new molecular mechanism for this process is proposed based on analogies with the mesophase and microsegregation behaviour of copolymers composed of rigid and flexible blocks. According to the model, α‐helical sequences play an essential role on the stabilization of fibrils. The model ought to apply to globular–fibrillar transformations occurring for other proteins and conformational incompatibility might play a role on the stability of native tertiary structures.

Acknowledgements

The author thanks Dr. Boris B. Akhremitchev, Duke University, for clarifying discussions; also Ing. Hesler Acevedo and Pedro Roman, Universidad San Carlos de Guatemala, for assistance in the assembly of the manuscript. Great appreciation is expressed to Profs. A.L. Crumbliss, K.Loos and M.M. Ripoll and to a referee for critically reading the manuscript.