Polyadenine complexed to polyglutamine suggests the peptide
backbone has a cis conformation
Anthony B. Bransgrove and Louise Amelia Anderson
The polyadenine (poly(A)) tail of mRNA is a homopolymer and as such is a potential H-bonding
partner for other cellular homopolymers. The secondary structure of proteins and peptides
employs the polar groups of the homopolymer backbone to bind with themselves or other
polymers to respectively form an alpha helix or a beta sheet. These same backbone polar groups
appear to be suitably positioned to bind with poly(A) but only when the backbone has rotated to
the all-cis conformation. However the all-cis conformation of peptides or proteins is rarely
encountered and so they would seem to be unlikely binding partners. Here we show that a
homopolymer of glutamine (poly(Q)) may be an exception to this rarity because its default
conformation seems to be all-cis. We found that exposure of poly(A) to increasing amounts of
poly(Q) causes a progressive loss of soluble poly(A) migrating on gel electrophoresis, indicating
binding between the two polymers. Stereochemical modelling of the likely complex has suggested
the particular polar groups that are responsible for binding of the two polymers, along with an
explanation for the all-cis conformation of poly(Q).
Keywords: carboxamide chain cooperativity, cis conformation of peptide backbone, mRNA
polyadenine tail, nascent peptides as target for polyadenine, neurodegenerative disease, peptide
bound adenine, polyglutamine aggregates, polyglutamine binding to promoter opens double helix.
