title: Role of Decorin Core Protein in Collagen Organisation in Congenital Stromal Corneal Dystrophy (CSCD).
abstract: The role of Decorin in organising the extracellular matrix was examined in normal human corneas and in corneas from patients with Congenital Stromal Corneal Dystrophy (CSCD). In CSCD, corneal clouding occurs due to a truncating mutation (c.967delT) in the decorin (DCN) gene. Normal human Decorin protein and the truncated one were reconstructed in silico using homology modelling techniques to explore structural changes in the diseased protein. Corneal CSCD specimens were also examined using 3-D electron tomography and Small Angle X-ray diffraction (SAXS), to image the collagen-proteoglycan arrangement and to quantify fibrillar diameters, respectively. Homology modelling showed that truncated Decorin had a different spatial geometry to the normal one, with the truncation removing a major part of the site that interacts with collagen, compromising its ability to bind effectively. Electron tomography showed regions of abnormal stroma, where collagen fibrils came together to form thicker fibrillar structures, showing that Decorin plays a key role in the maintenance of the order in the normal corneal extracellular matrix. Average diameter of individual fibrils throughout the thickness of the cornea however remained normal.
authors.affiliation: NCD-BL11, ALBA Synchrotron Light Source, Cerdanyola del Vallés, 08290, Barcelona, Spain.|Structural Biophysics Research Group, School of Optometry and Vision Sciences, Cardiff University, Cardiff, CF24 4HQ, United Kingdom.
authors.forename: Christina S
authors.initials: CS
authors.lastname: Kamma-Lorger
authors.affiliation: Structural Biophysics Research Group, School of Optometry and Vision Sciences, Cardiff University, Cardiff, CF24 4HQ, United Kingdom.
authors.forename: Christian
authors.initials: C
authors.lastname: Pinali
authors.affiliation: NCD-BL11, ALBA Synchrotron Light Source, Cerdanyola del Vallés, 08290, Barcelona, Spain.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Martínez
authors.affiliation: Structural Biophysics Research Group, School of Optometry and Vision Sciences, Cardiff University, Cardiff, CF24 4HQ, United Kingdom.
authors.forename: Jon
authors.initials: J
authors.lastname: Harris
authors.affiliation: Structural Biophysics Research Group, School of Optometry and Vision Sciences, Cardiff University, Cardiff, CF24 4HQ, United Kingdom.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Young
authors.affiliation: Department of Ophthalmology, Haukeland University Hospital, 5021 Bergen, Norway.
authors.forename: Cecilie
authors.initials: C
authors.lastname: Bredrup
authors.affiliation: NCD-BL11, ALBA Synchrotron Light Source, Cerdanyola del Vallés, 08290, Barcelona, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Crosas
authors.affiliation: NCD-BL11, ALBA Synchrotron Light Source, Cerdanyola del Vallés, 08290, Barcelona, Spain.
authors.forename: Marc
authors.initials: M
authors.lastname: Malfois
authors.affiliation: Department of Ophthalmology, Haukeland University Hospital, 5021 Bergen, Norway.|Department of Clinical Medicine, University of Bergen, 5020 Bergen, Norway.
authors.forename: Eyvind
authors.initials: E
authors.lastname: Rødahl
authors.affiliation: Structural Biophysics Research Group, School of Optometry and Vision Sciences, Cardiff University, Cardiff, CF24 4HQ, United Kingdom.
authors.forename: Keith M
authors.initials: KM
authors.lastname: Meek
authors.affiliation: Structural Biophysics Research Group, School of Optometry and Vision Sciences, Cardiff University, Cardiff, CF24 4HQ, United Kingdom.
authors.forename: Carlo
authors.initials: C
authors.lastname: Knupp
mesh_terms: D002810:Chondroitinases and Chondroitin Lyases / Q000378:metabolism; D003094:Collagen / Q000378:metabolism*; D003315:Cornea / Q000473:pathology; D003317:Corneal Dystrophies, Hereditary / Q000378:metabolism* / Q000473:pathology; D058575:Decorin / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D021621:Imaging, Three-Dimensional; D008958:Models, Molecular; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D055503:Protein Multimerization; D053838:Scattering, Small Angle; D040681:Structural Homology, Protein; D014054:Tomography; D014961:X-Ray Diffraction
chemical_list: C546878:DCN protein, human; D058575:Decorin; D050505:Mutant Proteins; D003094:Collagen; D002810:Chondroitinases and Chondroitin Lyases
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