A retroprotein has exactly the same sequence as a naturally-occurring protein, except that the direction in which the polypeptide backbone runs through the protein is exactly the opposite of what it was in the first place. In this paper, we reversed the direction of the entire backbone of cold shock protein A (CspA) from Escherichia coli. The sequence reversal, in this case, destroyed the folding information present in the sequence, but the tendency of the sequence to form a beta sheet-based structure remained conserved even after sequence reversal. Thus, retroCspA deposited as aggregates into readymade amyloid fibers, suggesting that one way to make designer amyloid fibers, e.g., for nanomaterial applications, would be to create retroproteins from several beta sheet-based proteins. While some of the retroproteins created in this manner would retain a certain level of folding information, and potentially fold into topologically mirror-imaged versions of the structures adopted by the original sequence(s), it is likely that other retroproteins would form amyloid fibers, since their sequences would be replete with beta sheet forming potential but without a folding route to a beta sheet-based globular protein structure. Such sequences would have a tendency to deposit into amyloid fibers.

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