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https://doi.org/10.1038/srep23836
DC Field | Value | |
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dc.title | PH Induced Conformational Transitions in the Transforming Growth Factor ?-Induced Protein (TGF?IP) Associated Corneal Dystrophy Mutants | |
dc.contributor.author | Murugan, E | |
dc.contributor.author | Venkatraman, A | |
dc.contributor.author | Lei, Z | |
dc.contributor.author | Mouvet, V | |
dc.contributor.author | Rui Yi Lim, R | |
dc.contributor.author | Muruganantham, N | |
dc.contributor.author | Goh, E | |
dc.contributor.author | Swee Lim Peh, G | |
dc.contributor.author | Beuerman, R.W | |
dc.contributor.author | Chaurasia, S.S | |
dc.contributor.author | Rajamani, L | |
dc.contributor.author | Mehta, J.S | |
dc.date.accessioned | 2020-10-31T11:37:45Z | |
dc.date.available | 2020-10-31T11:37:45Z | |
dc.date.issued | 2016 | |
dc.identifier.citation | Murugan, E, Venkatraman, A, Lei, Z, Mouvet, V, Rui Yi Lim, R, Muruganantham, N, Goh, E, Swee Lim Peh, G, Beuerman, R.W, Chaurasia, S.S, Rajamani, L, Mehta, J.S (2016). PH Induced Conformational Transitions in the Transforming Growth Factor ?-Induced Protein (TGF?IP) Associated Corneal Dystrophy Mutants. Scientific Reports 6 : 23836. ScholarBank@NUS Repository. https://doi.org/10.1038/srep23836 | |
dc.identifier.issn | 2045-2322 | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/182487 | |
dc.description.abstract | Most stromal corneal dystrophies are associated with aggregation and deposition of the mutated transforming growth factor-? induced protein (TGF?Ip). The 4 th-FAS1 domain of TGF?Ip harbors ?80% of the mutations that forms amyloidogenic and non-amyloidogenic aggregates. To understand the mechanism of aggregation and the differences between the amyloidogenic and non-amyloidogenic phenotypes, we expressed the 4 th-FAS1 domains of TGF?Ip carrying the mutations R555W (non-amyloidogenic) and H572R (amyloidogenic) along with the wild-type (WT). R555W was more susceptible to acidic pH compared to H572R and displayed varying chemical stabilities with decreasing pH. Thermal denaturation studies at acidic pH showed that while WT did not undergo any conformational transition, the mutants exhibited a clear pH-dependent irreversible conversion from ?? conformation to ?-sheet oligomers. The ?-oligomers of both mutants were stable at physiological temperature and pH. Electron microscopy and dynamic light scattering studies showed that ?-oligomers of H572R were larger compared to R555W. The ?-oligomers of both mutants were cytotoxic to primary human corneal stromal fibroblast (pHCSF) cells. The ?-oligomers of both mutants exhibit variations in their morphologies, sizes, thermal and chemical stabilities, aggregation patterns and cytotoxicities. | |
dc.publisher | Nature Publishing Group | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.source | Unpaywall 20201031 | |
dc.subject | amyloid protein | |
dc.subject | betaIG-H3 protein | |
dc.subject | recombinant protein | |
dc.subject | scleroprotein | |
dc.subject | transforming growth factor beta | |
dc.subject | amino acid sequence | |
dc.subject | cell survival | |
dc.subject | chemistry | |
dc.subject | congenital cornea dystrophy | |
dc.subject | cornea stroma | |
dc.subject | cytology | |
dc.subject | drug effects | |
dc.subject | Escherichia coli | |
dc.subject | fibroblast | |
dc.subject | gene expression | |
dc.subject | genetics | |
dc.subject | human | |
dc.subject | metabolism | |
dc.subject | molecular cloning | |
dc.subject | mutation | |
dc.subject | pathology | |
dc.subject | pH | |
dc.subject | primary cell culture | |
dc.subject | protein denaturation | |
dc.subject | protein domain | |
dc.subject | protein secondary structure | |
dc.subject | protein stability | |
dc.subject | Amino Acid Sequence | |
dc.subject | Amyloidogenic Proteins | |
dc.subject | Cell Survival | |
dc.subject | Cloning, Molecular | |
dc.subject | Corneal Dystrophies, Hereditary | |
dc.subject | Corneal Stroma | |
dc.subject | Escherichia coli | |
dc.subject | Extracellular Matrix Proteins | |
dc.subject | Fibroblasts | |
dc.subject | Gene Expression | |
dc.subject | Humans | |
dc.subject | Hydrogen-Ion Concentration | |
dc.subject | Mutation | |
dc.subject | Primary Cell Culture | |
dc.subject | Protein Denaturation | |
dc.subject | Protein Domains | |
dc.subject | Protein Stability | |
dc.subject | Protein Structure, Secondary | |
dc.subject | Recombinant Proteins | |
dc.subject | Transforming Growth Factor beta | |
dc.type | Article | |
dc.contributor.department | DUKE-NUS MEDICAL SCHOOL | |
dc.description.doi | 10.1038/srep23836 | |
dc.description.sourcetitle | Scientific Reports | |
dc.description.volume | 6 | |
dc.description.page | 23836 | |
dc.published.state | published | |
Appears in Collections: | Elements Staff Publications |
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