title: Biochemical properties and aggregation propensity of transforming growth factor-induced protein (TGFBIp) and the amyloid forming mutants.
abstract: TGFBI-associated corneal dystrophies are characterized by accumulation of insoluble deposits of the mutant protein transforming growth factor β-induced protein (TGFBIp) in the cornea. Depending on the nature of mutation, the lesions appear as granular (non-amyloid) or lattice lines (amyloid) in the Bowman's layer or in the stroma. This review article emphasizes the structural biology aspects of TGFBIp. We discuss the tinctorial properties and ultrastructure of deposits observed in granular and lattice corneal dystrophic mutants with amyloid and non-amyloid forms of other human protein deposition diseases and review the biochemical and putative functional role of the protein. Using bioinformatics tools, we identify intrinsic aggregation propensity and discuss the possible protective role of gatekeepers close to the "aggregation-prone" regions of native TGFBIp. We describe the relative aggregation rates of lattice corneal dystrophy (LCD) and granular corneal dystrophy (GCD2) mutants using the three-parameter model, which is based on intrinsic properties of polypeptide chains. The predictive power of this model is compared with two other algorithms. We conclude that the model is able to predict the aggregation rate of mutants which do not alter overall net charge of the protein. The need to understand the mechanism of corneal dystrophies from the structural biology viewpoint is emphasized.
authors.affiliation: Singapore Eye Research Institute, Singapore, Singapore; Duke-NUS SRP Neuroscience and Behavioral Disorders, Singapore, Singapore.
authors.forename: R
authors.initials: R
authors.lastname: Lakshminarayanan
authors.affiliation: Singapore Eye Research Institute, Singapore, Singapore; Duke-NUS SRP Neuroscience and Behavioral Disorders, Singapore, Singapore; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Shyam S
authors.initials: SS
authors.lastname: Chaurasia
authors.affiliation: Singapore Eye Research Institute, Singapore, Singapore.
authors.forename: Elavazhagan
authors.initials: E
authors.lastname: Murugan
authors.affiliation: Singapore Eye Research Institute, Singapore, Singapore.
authors.forename: Anandalakshmi
authors.initials: A
authors.lastname: Venkatraman
authors.affiliation: Singapore Eye Research Institute, Singapore, Singapore; Singapore National Eye Centre, Singapore, Singapore.
authors.forename: Shu-Ming
authors.initials: SM
authors.lastname: Chai
authors.affiliation: Singapore Eye Research Institute, Singapore, Singapore; Duke-NUS SRP Neuroscience and Behavioral Disorders, Singapore, Singapore; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Eranga N
authors.initials: EN
authors.lastname: Vithana
authors.affiliation: Singapore Eye Research Institute, Singapore, Singapore; Duke-NUS SRP Neuroscience and Behavioral Disorders, Singapore, Singapore; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Roger W
authors.initials: RW
authors.lastname: Beuerman
authors.affiliation: Singapore Eye Research Institute, Singapore, Singapore; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Singapore National Eye Centre, Singapore, Singapore; Department of Clinical Sciences, Duke-NUS Graduate Medical School, Singapore, Singapore. Electronic address: jodmehta@gmail.com.
authors.forename: Jodhbir S
authors.initials: JS
authors.lastname: Mehta
mesh_terms: D000682:Amyloid / Q000235:genetics* / Q000378:metabolism; D001669:Biochemical Phenomena; D003315:Cornea / Q000378:metabolism*; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D006801:Humans; D009154:Mutation; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism
chemical_list: D000682:Amyloid; D016212:Transforming Growth Factor beta; D004247:DNA
keywords: Chiti-Dobson equation; aggregation propensity; amyloid deposits; corneal dystrophies; protein aggregation