A cysteine-based molecular code informs collagen C-propeptide assembly
Author(s)DiChiara, Andrew Stephen; Li, Rasia C.; Suen, Patreece H.; Hosseini, Azade S.; Taylor, Rebecca J.; Weickhardt, Alexander F.; Malhotra, Diya; Shoulders, Matthew D.; ... Show more Show less
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Fundamental questions regarding collagen biosynthesis, especially with respect to the molecular origins of homotrimeric versus heterotrimeric assembly, remain unanswered. Here, we demonstrate that the presence or absence of a single cysteine in type-I collagen’s C-propeptide domain is a key factor governing the ability of a given collagen polypeptide to stably homotrimerize. We also identify a critical role for Ca2+ in non-covalent collagen C-propeptide trimerization, thereby priming the protein for disulfide-mediated covalent immortalization. The resulting cysteine-based code for stable assembly provides a molecular model that can be used to predict, a priori, the identity of not just collagen homotrimers, but also naturally occurring 2:1 and 1:1:1 heterotrimers. Moreover, the code applies across all of the sequence-diverse fibrillar collagens. These results provide new insight into how evolution leverages disulfide networks to fine-tune protein assembly, and will inform the ongoing development of designer proteins that assemble into specific oligomeric forms.
DepartmentMassachusetts Institute of Technology. Department of Chemistry; McGovern Institute for Brain Research at MIT
Springer Science and Business Media LLC
DiChiara, Andrew S. et al. “A cysteine-based molecular code informs collagen C-propeptide assembly.” Nature Communications 9 (2018): 4206 © 2018 The Author(s)
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