气候变化领域集成服务门户(CCPortal): Collagen’s enigmatic, highly conserved N-glycan has an essential proteostatic function

CCPortal

DOI	10.1073/pnas.2026608118
	Collagen’s enigmatic, highly conserved N-glycan has an essential proteostatic function
	Li R.C.; Wong M.Y.; DiChiara A.S.; Hosseini A.S.; Shoulders M.D.
发表日期	2021
ISSN	00278424
卷号	118 期号:10
英文摘要	Intracellular procollagen folding begins at the protein’s C-terminal propeptide (C-Pro) domain, which initiates triple-helix assembly and defines the composition and chain register of fibrillar collagen trimers. The C-Pro domain is later proteolytically cleaved and excreted from the body, while the mature triple helix is incorporated into the extracellular matrix. The procollagen C-Pro domain possesses a single N-glycosylation site that is widely conserved in all the fibrillar procollagens across humans and diverse other species. Given that the C-Pro domain is removed once procollagen folding is complete, the N-glycan might be presumed to be important for folding. Surprisingly, however, there is no difference in the folding and secretion of N-glycosylated versus non-N-glycosylated collagen type-I, leaving the function of the N-glycan unclear. We hypothesized that the collagen N-glycan might have a context-dependent function, specifically, that it could be required to promote procollagen folding only when proteostasis is challenged. We show that removal of the N-glycan from misfolding-prone C-Pro domain variants does indeed cause serious procollagen and ER proteostasis defects. The N-glycan promotes folding and secretion of destabilized C-Pro variants by providing access to the ER’s lectin-based chaperone machinery. Finally, we show that the C-Pro N-glycan is actually critical for the folding and secretion of even wild-type procollagen under ER stress conditions. Such stress is commonly incurred during development, wound healing, and other processes in which collagen production plays a key role. Collectively, these results establish an essential, context-dependent function for procollagen’s previously enigmatic N-glycan, wherein the carbohydrate moiety buffers procollagen folding against proteostatic challenge. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Calnexin and calreticulin; Collagen folding and proteostasis; ER protein folding; Extracellular matrix biosynthesis; N-glycosylation
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180331
作者单位	Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, United States
推荐引用方式 GB/T 7714	Li R.C.,Wong M.Y.,DiChiara A.S.,等. Collagen’s enigmatic, highly conserved N-glycan has an essential proteostatic function[J],2021,118(10).
APA	Li R.C.,Wong M.Y.,DiChiara A.S.,Hosseini A.S.,&Shoulders M.D..(2021).Collagen’s enigmatic, highly conserved N-glycan has an essential proteostatic function.Proceedings of the National Academy of Sciences of the United States of America,118(10).
MLA	Li R.C.,et al."Collagen’s enigmatic, highly conserved N-glycan has an essential proteostatic function".Proceedings of the National Academy of Sciences of the United States of America 118.10(2021).