Mammalian Functional Amyloid - The Functional Fold: Amyloid Structures in Nature - page 157

tight spatial and temporal control
to minimize toxic species
(compartmentalization and trafficking)

uncontrolled, loss of normal function
accumulation of toxic species

Figure 9.5 Functional amyloid can play a variety of roles and is highly

regulated. (a) Amyloid can refer to a diversity of structures that
have the cross-

β

-sheet fold; these range from relatively small
pre-fibrillar aggregates to fully formed fibres. Collectively, these
cross-

β

-sheet-rich structures have been shown to perform
a wide variety of physiological functions (black circles, top).
Given the fact that many polypeptides can form amyloid under
the right conditions, it is reasonable to expect that many more
instances of functional amyloid are likely to be identified (black
circles, bottom). (b) Functional and pathological amyloids
share a common cross-

β

structure and, presumably, a common
assembly mechanism. In the case of Pmel17, amyloidogenesis
is highly regulated in both space and time to prevent toxicity,
whereas pathological amyloidogenesis is uncontrolled and
leads to accumulation of toxic species.

Acknowledgement

This work was supported by the National Institutes of Health
(GM42336 and GM33301 to WEB and AG18917 to JWK and WEB).
AVK is a Fellow of the Cystic Fibrosis Foundation.