Format

Send to

Choose Destination
Structure. 2017 Nov 7;25(11):1740-1750.e2. doi: 10.1016/j.str.2017.09.001. Epub 2017 Oct 5.

Structural and Functional Implications of Human Transforming Growth Factor β-Induced Protein, TGFBIp, in Corneal Dystrophies.

Author information

1
Proteolysis Laboratory, Structural Biology Unit ("María-de-Maeztu" Unit of Excellence), Molecular Biology Institute of Barcelona (CSIC), Barcelona Science Park, c/Baldiri Reixac 15-21, 08028 Barcelona, Catalonia, Spain.
2
Department of Molecular Biology and Genetics, Aarhus University, Gustav Wieds Vej, 10, 8000 Aarhus C, Denmark.
3
Proteolysis Laboratory, Structural Biology Unit ("María-de-Maeztu" Unit of Excellence), Molecular Biology Institute of Barcelona (CSIC), Barcelona Science Park, c/Baldiri Reixac 15-21, 08028 Barcelona, Catalonia, Spain. Electronic address: xgrcri@ibmb.csic.es.

Abstract

A major cause of visual impairment, corneal dystrophies result from accumulation of protein deposits in the cornea. One of the proteins involved is transforming growth factor β-induced protein (TGFBIp), an extracellular matrix component that interacts with integrins but also produces corneal deposits when mutated. Human TGFBIp is a multi-domain 683-residue protein, which contains one CROPT domain and four FAS1 domains. Its structure spans ∼120 Å and reveals that vicinal domains FAS1-1/FAS1-2 and FAS1-3/FAS1-4 tightly interact in an equivalent manner. The FAS1 domains are sandwiches of two orthogonal four-stranded β sheets decorated with two three-helix insertions. The N-terminal FAS1 dimer forms a compact moiety with the structurally novel CROPT domain, which is a five-stranded all-β cysteine-knot solely found in TGFBIp and periostin. The overall TGFBIp architecture discloses regions for integrin binding and that most dystrophic mutations cluster at both molecule ends, within domains FAS1-1 and FAS1-4.

KEYWORDS:

corneal dystrophy; crystal structure; cysteine-rich CROPT domain; extracellular matrix protein; fasciclin FAS1 domain; multi-domain protein; pathological mutants

PMID:
28988748
DOI:
10.1016/j.str.2017.09.001
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center