Structure-based prediction reveals capping motifs that inhibit beta-helix aggregation
Author(s)Bryan, Allen W.; Starner-Kreinbrink, Jennifer L.; Hosur, Raghavendra; Clark, Patricia L.; Berger, Bonnie
Structure-based prediction reveals capping motifs that inhibit β-helix aggregation
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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.
DepartmentHarvard 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
Proceedings of the National Academy of Sciences of the United States of America
National Academy of Sciences (U.S.)
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.
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