title: Effect of helical flanking sequences on the morphology of polyglutamine-containing fibrils.
abstract: A peptide model system has been developed to study the effects of helical flanking sequences on polyglutamine aggregation. In a companion manuscript, the kinetics of aggregation are described, comparing the influence of a well-defined heterotetrameric coiled coil to that of the helix-rich structure found in Htt(NT), a 17-residue flanking sequence found in the huntingtin protein, on polyglutamine aggregation. Here, the morphological characterization of the resultant fibrils that form for a set of peptides is reported, only one of which, KKQ25KK, has been previously studied. A careful analysis of TEM and AFM images of KKQ25KK confirms that it forms bundled fibrils of varying length and reveals, unexpectedly, that they are composed of fully extended cross-β-strands. Second, it is shown that helical flanking sequences do not disrupt the assembly of a core cross-β-sheet structure, but such flanking sequences can influence higher order processes, such as inhibiting the bundling of the fibrils.
authors.affiliation: Department of Biology, Haverford College , 370 Lancaster Avenue, Haverford, Pennsylvania 19041, United States.
authors.forename: Bashkim
authors.initials: B
authors.lastname: Kokona
authors.forename: Karl A
authors.initials: KA
authors.lastname: Johnson
authors.forename: Robert
authors.initials: R
authors.lastname: Fairman
mesh_terms: D006801:Humans; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D066329:Protein Aggregates; D017433:Protein Structure, Secondary
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D010455:Peptides; D066329:Protein Aggregates; C097188:polyglutamine