The World of Functional Amyloid - The Functional Fold: Amyloid Structures in Nature - page 9

Given the relative simplicity of the amyloid fold, amyloid fibres
are able to take on a stunningly wide range of functions. In bacteria,
algae, and insect eggshells, amyloid fibres play a structural role;
they enable colony formation, protect the organisms from the
environment, and facilitate surface adhesion.

1,29,31

Amyloid has also
been proposed to comprise the structure of spider silk, which has
incredible mechanical strength.

30

Fungal amyloid fibres serve as
epigenetic elements that function as drivers of phenotypic diversity
and heterokaryon incompatibility.

49

In mammals, amyloid functions
to facilitate the synthesis of melanin while mitigating the inherent
chemotoxicity of melanin formation.

32

Furthermore, amyloid-like
motifs could be important for regulating human hemostasis.

50
To take advantage of amyloid for biological function, cellular and
biochemical regulation is important to avoid toxicity.

51

Organisms
appear to have evolved unique methods for regulating the amyloid
formation process to avoid toxicity, although some common themes
exist. For example, in the formation of curli amyloid

fibres appears to be nucleated by the CsgB protein outside the
cell.

Escherichia coli

50

regulate prion amyloid formation
with an intracellular chaperone network.

Saccharomyces cerevisiae

49,50,52

Functional amyloid
in humans appears to be regulated both by proteolysis to release
the fibrillogenic fragment and by extremely rapid polymerization
kinetics to prevent exposure of the cell to potentially toxic species.

50

In general, functional amyloid structures are found either outside
the cell or contained within membrane-delimited vesicles.

50

This
physical sequestration of amyloid presumably serves to protect the
cell. All these regulatory schemes are likely necessary to avoid the
toxicity of amyloid formation.
Amyloid seems likely to have appeared relatively early in
evolutionary terms. Many polypeptide sequences can form amyloid
under appropriate conditions, and functional amyloid is found in
organisms ranging from bacteria to humans. Additionally, studies
of the

spp. Sup35 prion protein suggest that the
capacity for amyloid formation has been conserved for hundreds
of millions of years.

Saccharomyces

53

These observations, combined with the fact
that amyloidogenic proteins share little in the way of sequence or
structural homology, suggests that amyloid is a primitive structure
that likely existed for as long as living organisms have used
polypeptides. Given its utility, simplicity, and self-seeding mechanism
of formation, amyloid could have been a prominent fold early in the
evolution of life.