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Corneal dystrophy mutations drive pathogenesis by targeting TGFBIp stability and solubility in a latent amyloid-forming domain

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Corneal dystrophy mutations drive pathogenesis by targeting TGFBIp stability and solubility in a latent amyloid-forming domain. / Stenvang, Marcel; Schafer, Nicholas P; Malmos, Kirsten Gade; Pérez, Adriana-Michelle Wolf; Niembro, Olatz; Sormanni, Pietro; Basaiawmoit, Rajiv Vaid; Christiansen, Gunna; Andreasen, Maria; Otzen, Daniel E.

I: Journal of Molecular Biology, Bind 430, Nr. 8, 13.04.2018, s. 1116-1140.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Harvard

Stenvang, M, Schafer, NP, Malmos, KG, Pérez, A-MW, Niembro, O, Sormanni, P, Basaiawmoit, RV, Christiansen, G, Andreasen, M & Otzen, DE 2018, 'Corneal dystrophy mutations drive pathogenesis by targeting TGFBIp stability and solubility in a latent amyloid-forming domain', Journal of Molecular Biology, bind 430, nr. 8, s. 1116-1140. https://doi.org/10.1016/j.jmb.2018.03.001

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MLA

Vancouver

Stenvang M, Schafer NP, Malmos KG, Pérez A-MW, Niembro O, Sormanni P o.a. Corneal dystrophy mutations drive pathogenesis by targeting TGFBIp stability and solubility in a latent amyloid-forming domain. Journal of Molecular Biology. 2018 apr 13;430(8):1116-1140. https://doi.org/10.1016/j.jmb.2018.03.001

Author

Stenvang, Marcel ; Schafer, Nicholas P ; Malmos, Kirsten Gade ; Pérez, Adriana-Michelle Wolf ; Niembro, Olatz ; Sormanni, Pietro ; Basaiawmoit, Rajiv Vaid ; Christiansen, Gunna ; Andreasen, Maria ; Otzen, Daniel E. / Corneal dystrophy mutations drive pathogenesis by targeting TGFBIp stability and solubility in a latent amyloid-forming domain. I: Journal of Molecular Biology. 2018 ; Bind 430, Nr. 8. s. 1116-1140.

Bibtex

@article{0ffe407a07bf4dcd9f9bab0836d98b50,
title = "Corneal dystrophy mutations drive pathogenesis by targeting TGFBIp stability and solubility in a latent amyloid-forming domain",
abstract = "Numerous mutations in the corneal protein TGFBIp lead to opaque extracellular deposits and corneal dystrophies (CDs). Here we elucidate the molecular origins underlying TGFBIp's mutation-induced increase in aggregation propensity through comprehensive biophysical and bioinformatic analyses of mutations associated with every major subtype of TGFBIp-linked CDs including lattice corneal dystrophy (LCD) and three subtypes of granular corneal dystrophy (GCD 1-3). LCD mutations at buried positions in the C-terminal Fas1-4 domain lead to decreased stability. GCD variants show biophysical profiles distinct from those of LCD mutations. GCD 1 and 3 mutations reduce solubility rather than stability. Half of the 50 positions within Fas1-4 most sensitive to mutation are associated with at least one known disease-causing mutation, including 10 of the top 11 positions. Thus, TGFBIp aggregation is driven by mutations that despite their physico-chemical diversity target either the stability or solubility of Fas1-4 in predictable ways, suggesting straightforward general therapeutic strategies.",
author = "Marcel Stenvang and Schafer, {Nicholas P} and Malmos, {Kirsten Gade} and P{\'e}rez, {Adriana-Michelle Wolf} and Olatz Niembro and Pietro Sormanni and Basaiawmoit, {Rajiv Vaid} and Gunna Christiansen and Maria Andreasen and Otzen, {Daniel E}",
note = "Copyright {\textcopyright} 2018. Published by Elsevier Ltd.",
year = "2018",
month = apr,
day = "13",
doi = "10.1016/j.jmb.2018.03.001",
language = "English",
volume = "430",
pages = "1116--1140",
journal = "Journal of Molecular Biology",
issn = "0022-2836",
publisher = "Academic Press",
number = "8",

}

RIS

TY - JOUR

T1 - Corneal dystrophy mutations drive pathogenesis by targeting TGFBIp stability and solubility in a latent amyloid-forming domain

AU - Stenvang, Marcel

AU - Schafer, Nicholas P

AU - Malmos, Kirsten Gade

AU - Pérez, Adriana-Michelle Wolf

AU - Niembro, Olatz

AU - Sormanni, Pietro

AU - Basaiawmoit, Rajiv Vaid

AU - Christiansen, Gunna

AU - Andreasen, Maria

AU - Otzen, Daniel E

N1 - Copyright © 2018. Published by Elsevier Ltd.

PY - 2018/4/13

Y1 - 2018/4/13

N2 - Numerous mutations in the corneal protein TGFBIp lead to opaque extracellular deposits and corneal dystrophies (CDs). Here we elucidate the molecular origins underlying TGFBIp's mutation-induced increase in aggregation propensity through comprehensive biophysical and bioinformatic analyses of mutations associated with every major subtype of TGFBIp-linked CDs including lattice corneal dystrophy (LCD) and three subtypes of granular corneal dystrophy (GCD 1-3). LCD mutations at buried positions in the C-terminal Fas1-4 domain lead to decreased stability. GCD variants show biophysical profiles distinct from those of LCD mutations. GCD 1 and 3 mutations reduce solubility rather than stability. Half of the 50 positions within Fas1-4 most sensitive to mutation are associated with at least one known disease-causing mutation, including 10 of the top 11 positions. Thus, TGFBIp aggregation is driven by mutations that despite their physico-chemical diversity target either the stability or solubility of Fas1-4 in predictable ways, suggesting straightforward general therapeutic strategies.

AB - Numerous mutations in the corneal protein TGFBIp lead to opaque extracellular deposits and corneal dystrophies (CDs). Here we elucidate the molecular origins underlying TGFBIp's mutation-induced increase in aggregation propensity through comprehensive biophysical and bioinformatic analyses of mutations associated with every major subtype of TGFBIp-linked CDs including lattice corneal dystrophy (LCD) and three subtypes of granular corneal dystrophy (GCD 1-3). LCD mutations at buried positions in the C-terminal Fas1-4 domain lead to decreased stability. GCD variants show biophysical profiles distinct from those of LCD mutations. GCD 1 and 3 mutations reduce solubility rather than stability. Half of the 50 positions within Fas1-4 most sensitive to mutation are associated with at least one known disease-causing mutation, including 10 of the top 11 positions. Thus, TGFBIp aggregation is driven by mutations that despite their physico-chemical diversity target either the stability or solubility of Fas1-4 in predictable ways, suggesting straightforward general therapeutic strategies.

U2 - 10.1016/j.jmb.2018.03.001

DO - 10.1016/j.jmb.2018.03.001

M3 - Journal article

C2 - 29524512

VL - 430

SP - 1116

EP - 1140

JO - Journal of Molecular Biology

JF - Journal of Molecular Biology

SN - 0022-2836

IS - 8

ER -