Structure-based prediction reveals capping motifs that inhibit [Beta]-helix aggregation

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...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2011-07, Vol.108 (27), p.11099
Main Authors: Bryan, Allen W, Starner-Kreinbrink, Jennifer L, Hosur, Raghavendra, Clark, Patricia L, Berger, Bonnie
Format: Article
Language:English
Subjects:
Bacteria
Bacterial proteins
Cells
Molecular structure
Vertebrates
Online Access:Get full text
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Summary: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. [PUBLICATION ABSTRACT]
ISSN:0027-8424
1091-6490