Department of Chemistry, Rice University, Houston, TX, USA.
Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA, USA.
Nat Commun. 2024 Nov 29;15(1):10385. doi: 10.1038/s41467-024-54560-z.
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.
从头设计自组装肽在科学研究中受到了极大关注。虽然α-螺旋组装已经得到了广泛研究，但对胶原蛋白中存在的聚脯氨酸 II 型螺旋的探索仍然相对有限。在这项研究中，我们以防御性胶原蛋白表面活性蛋白 A 为模型，专注于理解胶原样肽分级组装中的序列-结构关系。通过剖析源自表面活性蛋白 A 的序列并合成短的胶原样肽，我们成功构建了离散的空心三聚体螺旋束。氨基酸取代研究确定了对寡聚体形成至关重要的疏水性和带电残基。这些见解指导了胶原样肽的从头设计，导致形成了多种四级结构，包括离散和异质的束状寡聚物、二维纳米片和 pH 响应性纳米带。我们的研究代表了在理解和利用胶原高级组装方面的重大进展，超越了三聚体螺旋。
