Collagen is prevalent in connective tissues where it plays major roles in homeostasis, wound healing, tissue regeneration and cancer. Understanding the structure and assembly mechanism of collagen is crucial for biological applications and design of new supramolecular self-assembly systems based on this motif. Collagen undergoes a beautiful hierarchical assembly starting from peptides to form a triple helix which can pack into fibril bundles and subsequently into larger fibers. Triple helix structure has been extensively studied,but packing of triple helices into helical bundles is poorly understood due to the lack of atomic level structural information and available models. Our approach is to study proteins which contain collagen-like domains but are not included in the traditional collagen family such as complement component 1q (C1q) and pulmonary surfactant protein A (SP-A). These proteins have a bouquet structure that contains a collagenous stem and branches. We expect the stem helical bundle will inform interhelical assembly while the branching triple helices will inform intrahelical assembly with a new range of pairwise amino acid interactions. In this presentation, I describe our progress toward understanding triple helical bundling based on the stem region of C1q and SP-A with the self-assembly of synthetic peptides. Circular dichroism spectroscopy confirmed the formation of a stable triple helix; size exclusion chromatography and ultracentrifugation support triple helices oligomerized into an 18-mer completely independent of the globular domain. Efforts at structure determination by crystallization are ongoing but have already yielded low resolution data of the native assembly along with seleno-methionine and iodo-phenylalaline derivatives. This structural study will give valuable information about these critically important defense collagens as well as about traditional collagen self-assembly hierarchy.

Study of the self-assembly of defense collagens: Trimers and higher-order oligomers

ACS Spring 2022

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