Structure-based prediction reveals capping motifs that inhibit beta-helix aggregation
Name
A. W. Bryan-2011-May-Structure-based pred.pdf
Size
1.7 MB
Format
Adobe PDF
Checksum (MD5)
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Author(s)
Bryan, Allen W.
Starner-Kreinbrink, Jennifer L.
Hosur, Raghavendra
Clark, Patricia L.
Berger, Bonnie
Alternative Title
Structure-based prediction reveals capping motifs that inhibit β-helix aggregation
Date Issued
July 2011
Journal
Proceedings of the National Academy of Sciences of the United States of America
Publisher
National Academy of Sciences (U.S.)
Citation
Bryan, A. W. et al. “Structure-based prediction reveals capping motifs that inhibit beta-helix aggregation.” Proceedings of the National Academy of Sciences 108.27 (2011): 11099-11104.
Version
Final published version
Abstract
The parallel beta-helix is a geometrically regular fold commonly found in the proteomes of bacteria, viruses, fungi, archaea, and some vertebrates. beta-helix structure has been observed in monomeric units of some aggregated amyloid fibers. In contrast, soluble beta-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 beta-helix cap structures reveals subtle commonalities in structural components and in interactions with the beta-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 beta-helix resulted in increased aggregation and the formation of soluble oligomeric species. These results suggest that beta-helix cap motifs can prevent specific, beta-sheet-mediated oligomeric interactions, similar to those observed in amyloid formation.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory
Massachusetts Institute of Technology. Department of Materials Science and Engineering
Massachusetts Institute of Technology. Department of Mathematics
Whitehead Institute for Biomedical Research
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1073/pnas.1017504108
