Silkmoth Chorion: A Natural Protective Amyloid - The Functional Fold: Amyloid Structures in Nature - page 65

At this point, it is relevant to mention how amyloid fibrillo-
genesis of silkmoth chorion protein peptide-analogues is actually
performed. The phenomenon of the transformation of proteins
into amyloid fibrils is of interest, not only because it is related to
the protein folding problem, but also, because it is connected to the
so-called conformational diseases, the amyloidoses. Consequently,
various attempts have been directed towards an understanding of
the fibrillogenesis pathway(s), with the aim of developing inhibitor
drugs of therapeutic benefit. These are summarized in several
excellent recent reviews.

6,25-29

However, the molecular and energetic
factors affecting protein misfolding and amyloid fibrillogenesis are
still largely unknown.

28,30
Recently, we presented data, which clearly show that the first
main step of amyloid-like fibrillogenesis from silk moth chorion
peptides is the formation of nuclei of liquid crystalline nature.

18

Subsequently, these liquid-crystalline nuclei “collapse” and they are
transformed into amyloid-like fibrils in a time period, that depends
on several factors. The transformation is performed, most probably,
as a result of a conformational transition to the structure of chorion
peptides, from a left-handed parallel

β

-helix to an antiparallel

β

-pleated sheet (Iconomidou, Chryssikos, Gionis, and Hamodrakas,
in preparation). Chorion peptides, apparently, have been designed to
play this role after millions of years of molecular evolution.

4.3 Model Structure of Silkmoth Chorion

Amyloidogenic Peptides

Taking into account all experimental and theoretical evidence
accumulated previously for silkmoth chorion proteins

12

and their

5,9,17

synthetic peptide analogues, and the hexapeptide periodicities

in the sequences of the A and B families of silkmoth chorion
proteins,

31,32

the models shown in Figs. 4.11 and 4.12 for the peptide
cA are the most probable models for the structure of silkmoth
chorion peptides. The model shown in Fig. 4.11 is an antiparallel
twisted

β β

-pleated sheet of four-residue -strands alternating with

type II' -turns. Invariant glyceine residues occupy the second

position of the

β

-turns, a location especially favourable for glyceine
in II' turns of twisted

β

33

β

-sheets of globular proteins.