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|a DiChiara, Andrew Stephen
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|a Massachusetts Institute of Technology. Department of Chemistry
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|a McGovern Institute for Brain Research at MIT
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|a Li, Rasia C.
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|a Suen, Patreece H.
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|a Hosseini, Azade S.
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|a Taylor, Rebecca J.
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|a Weickhardt, Alexander F.
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|a Malhotra, Diya
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|a Shoulders, Matthew D.
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|a A cysteine-based molecular code informs collagen C-propeptide assembly
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|b Springer Science and Business Media LLC,
|c 2020-05-28T17:31:58Z.
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|z Get fulltext
|u https://hdl.handle.net/1721.1/125561
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|a 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.
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|a National Science Foundation (U.S.) (Grant NSF-0070319)
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|a National Science Foundation (U.S.). Center for Science of Information (Grant P30-ES002109)
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|a National Institutes of Health (U.S.) (Grant R03AR067503)
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|a National Institutes of Health (U.S.) (Grant 1R01AR071443)
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|a National Institutes of Health (U.S.). Ruth Kirschstein Predoctoral Fellowship (1F31AR067615)
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|a en
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|a Article
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|t Nature Communications
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