title: Structure-based prediction reveals capping motifs that inhibit β-helix aggregation.
abstract: The parallel β-helix is a geometrically regular fold commonly found in the proteomes of bacteria, viruses, fungi, archaea, and some vertebrates. β-helix structure has been observed in monomeric units of some aggregated amyloid fibers. In contrast, soluble β-helices, both right- and left-handed, are usually "capped" on each end by one or more secondary structures. Here, an in-depth classification of the diverse range of β-helix cap structures reveals subtle commonalities in structural components and in interactions with the β-helix core. Based on these uncovered commonalities, a toolkit of automated predictors was developed for the two distinct types of cap structures. In vitro deletion of the toolkit-predicted C-terminal cap from the pertactin β-helix resulted in increased aggregation and the formation of soluble oligomeric species. These results suggest that β-helix cap motifs can prevent specific, β-sheet-mediated oligomeric interactions, similar to those observed in amyloid formation.
authors.affiliation: Harvard-Massachusetts Institute of Technology (MIT) Division of Health Sciences and Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors.forename: Allen W
authors.initials: AW
authors.lastname: Bryan
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Starner-Kreinbrink
authors.forename: Raghavendra
authors.initials: R
authors.lastname: Hosur
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Clark
authors.forename: Bonnie
authors.initials: B
authors.lastname: Berger
mesh_terms: D000595:Amino Acid Sequence; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000235:genetics; D055592:Biophysical Phenomena; D003198:Computer Simulation; D030562:Databases, Protein; D008390:Markov Chains; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017510:Protein Folding; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D010566:Virulence Factors, Bordetella / Q000737:chemistry / Q000235:genetics
chemical_list: D001425:Bacterial Outer Membrane Proteins; D011506:Proteins; D010566:Virulence Factors, Bordetella; C068929:pertactin