Curli Extracellular Matrix - The Functional Fold: Amyloid Structures in Nature - page 122

the aggregation process (even after few minutes of incubation) in
the form of monomers or dimers at the most, as determined by size
exclusion chromatography. This finding led to two conclusions: (i)
CsgA shares common polymerization intermediate with eukaryotic
amyloids; (ii) CsgA has a strong predisposition toward formation
of fibrillar structures, which apparently is encoded in its primary
structure.
The innate tendency of CsgA to fibrillize is hypothesized to stem
from the intramolecular repeats comprising its sequence, each acting
as an independent amyloidogenic domain. Five repeating units

are included in the sequence of CsgA (and CsgB). These repeats, 19-23
amino acids in length, share 30% identity and contain four conserved
polar residues of serine, glutamine, or asparagine every 5-7 amino
acids (Fig. 7.3a). Computer homology modelling suggests that the
repeats encode for five strand-loop-strand motifs that together
fold into parallel

30,32,34

β

30,35

-helix structure of the monomer (Fig. 7.3b).

Accordingly, the structure is stabilized by a hydrophobic core and
hydrogen bonds that occur between the conserved polar residues
located at the tips of the turns in each repeating unit. Each turn
region comprises conserved glycine residues to allow the necessary
conformational flexibility, in addition to conserved aromatic
residues (tyrosine, phenylalanine, or histidine) hypothesized to
mediate interaction between turns regions.

34

In fact, the hexapeptide
repeating sequences, composed of the turn sequence along with two
flanking polar residues (glutamine or asparagine), were suggested
to represent a minimal amyloidogenic motif, as they were shown
to be sufficient to amyloid-like fibrillization.

34

The strand-loop-
strand motif rather resembles the pair-of-sheets organization of
the cross

-spine structure described for many disease-associated
amyloids and fibril forming segments.

β

suggested
that the repeating units actually represent amyloidogenic domains,
allowing efficient self-complementation and transition from soluble
protein to amyloid fibre. This might explain the early recognition of
intermediate-like conformations by A11 antibodies.

36,37

Wang et al .

32

32

7.4.3 In Vivo Curli Polymerization: Extracellular

Nucleation-Precipitation Model

The process of curli biogenesis is believed to occur outside the
bacterial cell through a proposed mechanism called extracellular
nucleation-precipitation (ENP). According to the ENP hypothesis,