当前位置： SCI文献检索 > JOURNAL OF MOLECULAR BIOLOGY期刊下所有文献 > The Changing Face of Aging: Highly Sulfated Glycosaminoglycans Induce Amyloid Formation in a Lattice Corneal Dystrophy Model Protein.

The Changing Face of Aging: Highly Sulfated Glycosaminoglycans Induce Amyloid Formation in a Lattice Corneal Dystrophy Model Protein.

Abstract：

:Glycosaminoglycans (GAGs) are related to multiple biological functions and diseases. There is growing evidence that GAG concentration and sulfate content increase with age. The destabilizing mutation A546T in the corneal protein TGFBIp leads to lattice-type corneal dystrophy, but symptoms only appear in the fourth decade of life. We hypothesize that this delayed phenotype can be explained by increased GAG sulfation over time. Using in vitro assays with the C-terminal TGFIBIp domain Fas1-4, previously shown to recapitulate many properties of full-length TGFBIp, we find that only long GAGs with multiple sulfate groups on each repeating unit increase the amount of worm-like aggregates and induce long, straight fibrils in A546T. In contrast, GAGs did not induce aggregation of wildtype Fas1-4, suggesting that the finding might be specific for lattice corneal dystrophy mutants. Our results highlight a possible role of changing GAG sulfation in the accumulation of amyloid, which also may have implications for the development of neurodegenerative diseases.

journal_name

J Mol Biol

journal_title

Journal of molecular biology

authors

Malmos KG,Stenvang M,Sahin C,Christiansen G,Otzen DE

doi

10.1016/j.jmb.2017.07.014

subject

Has Abstract

pub_date

2017-09-01 00:00:00

pages

2755-2764

issue

18

eissn

0022-2836

issn

1089-8638

pii

S0022-2836(17)30351-0

journal_volume

429

pub_type

杂志文章

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