TY - JOUR
T1 - Structural and Functional Implications of Human Transforming Growth Factor β-Induced Protein, TGFBIp, in Corneal Dystrophies
AU - García-Castellanos, Raquel
AU - Nielsen, Nadia Sukusu
AU - Runager, Kasper
AU - Thøgersen, Ida B
AU - Lukassen, Marie V
AU - Poulsen, Ebbe T
AU - Goulas, Theodoros
AU - Enghild, Jan J
AU - Gomis-Rüth, F Xavier
N1 - Copyright © 2017 Elsevier Ltd. All rights reserved.
PY - 2017/11/7
Y1 - 2017/11/7
N2 - 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. García-Castellanos et al. report the structure of transforming growth factor β-induced protein (TGFBIp), a corneal component. When mutated, TGFBIp accumulates and causes corneal dystrophies and vision impairment. The elongated structure of TGFBIp comprises one CROPT and four FAS1 domains, and most dystrophic mutations cluster within terminal domains FAS1-1 and FAS1-4.
AB - 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. García-Castellanos et al. report the structure of transforming growth factor β-induced protein (TGFBIp), a corneal component. When mutated, TGFBIp accumulates and causes corneal dystrophies and vision impairment. The elongated structure of TGFBIp comprises one CROPT and four FAS1 domains, and most dystrophic mutations cluster within terminal domains FAS1-1 and FAS1-4.
KW - Journal Article
UR - http://www.scopus.com/inward/record.url?scp=85030623160&partnerID=8YFLogxK
U2 - 10.1016/j.str.2017.09.001
DO - 10.1016/j.str.2017.09.001
M3 - Journal article
C2 - 28988748
SN - 0969-2126
VL - 25
SP - 1740-1750.e2
JO - Structure
JF - Structure
IS - 11
ER -