Structure of a Functional Amyloid Protein Subunit Computed Using Sequence Variation

Functional amyloid fibers, called
curli, play a critical role in
adhesion and invasion of many bacteria. Unlike pathological amyloids,
curli structures are formed by polypeptide sequences whose amyloid
structure has been selected for during evolution. This important distinction
provides us with an opportunity to obtain structural insights from
an unexpected source: the covariation of amino acids in sequences
of different curli proteins. We used recently developed methods to
extract amino acid contacts from a multiple sequence alignment of
homologues of the curli subunit protein, CsgA. Together with an efficient
force field, these contacts allow us to determine structural models
of CsgA. We find that CsgA forms a β-helical structure, where
each turn corresponds to previously identified repeat sequences in
CsgA. The proposed structure is validated by previously measured solid-state
NMR, electron microscopy, and X-ray diffraction data and agrees with
an earlier proposed model derived by complementary means.