A cysteine-based molecular code informs collagen C-propeptide assembly

Andrew S. DiChiara, Rasia C. Li, Patreece H. Suen, Azade S. Hosseini, Rebecca J. Taylor, Alexander F. Weickhardt, Diya Malhotra, Darrell R. McCaslin and Matthew D. Shoulders ()
Additional contact information
Andrew S. DiChiara: Massachusetts Institute of Technology
Rasia C. Li: Massachusetts Institute of Technology
Patreece H. Suen: Massachusetts Institute of Technology
Azade S. Hosseini: Massachusetts Institute of Technology
Rebecca J. Taylor: Massachusetts Institute of Technology
Alexander F. Weickhardt: Massachusetts Institute of Technology
Diya Malhotra: Massachusetts Institute of Technology
Darrell R. McCaslin: University of Wisconsin
Matthew D. Shoulders: Massachusetts Institute of Technology

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: Abstract 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.

Date: 2018
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-018-06185-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06185-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-06185-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().