Exploration of the hierarchical assembly space of collagen-like peptides beyond the triple helix

Abstract The de novo design of self-assembling peptides has garnered significant attention in scientific research. While alpha-helical assemblies have been extensively studied, exploration of polyproline type II helices, such as those found in collagen, remains relatively limited. In this study, we...

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Bibliographic Details
Main Authors: Le Tracy Yu, Mark A. B. Kreutzberger, Thi H. Bui, Maria C. Hancu, Adam C. Farsheed, Edward H. Egelman, Jeffrey D. Hartgerink
Format: Article
Language:English
Published: Nature Portfolio 2024-11-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-024-54560-z
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Summary:Abstract The de novo design of self-assembling peptides has garnered significant attention in scientific research. While alpha-helical assemblies have been extensively studied, exploration of polyproline type II helices, such as those found in collagen, remains relatively limited. In this study, we focus on understanding the sequence-structure relationship in hierarchical assemblies of collagen-like peptides, using defense collagen Surfactant Protein A as a model. By dissecting the sequence derived from Surfactant Protein A and synthesizing short collagen-like peptides, we successfully construct a discrete bundle of hollow triple helices. Amino acid substitution studies pinpoint hydrophobic and charged residues that are critical for oligomer formation. These insights guide the de novo design of collagen-like peptides, resulting in the formation of diverse quaternary structures, including discrete and heterogenous bundled oligomers, two-dimensional nanosheets, and pH-responsive nanoribbons. Our study represents a significant advancement in the understanding and harnessing of collagen higher-order assemblies beyond the triple helix.
ISSN:2041-1723