+Open data
-Basic information
Entry | Database: PDB / ID: 6fd8 | ||||||
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Title | Gamma-s crystallin dimer | ||||||
Components | Beta-crystallin S | ||||||
Keywords | STRUCTURAL PROTEIN / Crystallin / eye lens / vision / cataract. | ||||||
Function / homology | Function and homology information structural constituent of eye lens / lens development in camera-type eye / visual perception / morphogenesis of an epithelium Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.1 Å | ||||||
Authors | Mabbitt, P.D. / Thorn, D.C. / Jackson, C.J. / Carver, J.A. | ||||||
Citation | Journal: J Mol Biol / Year: 2019 Title: The Structure and Stability of the Disulfide-Linked γS-Crystallin Dimer Provide Insight into Oxidation Products Associated with Lens Cataract Formation. Authors: David C Thorn / Aidan B Grosas / Peter D Mabbitt / Nicholas J Ray / Colin J Jackson / John A Carver / Abstract: The reducing environment in the eye lens diminishes with age, leading to significant oxidative stress. Oxidation of lens crystallin proteins is the major contributor to their destabilization and ...The reducing environment in the eye lens diminishes with age, leading to significant oxidative stress. Oxidation of lens crystallin proteins is the major contributor to their destabilization and deleterious aggregation that scatters visible light, obscures vision, and ultimately leads to cataract. However, the molecular basis for oxidation-induced aggregation is unknown. Using X-ray crystallography and small-angle X-ray scattering, we describe the structure of a disulfide-linked dimer of human γS-crystallin that was obtained via oxidation of C24. The γS-crystallin dimer is stable at glutathione concentrations comparable to those in aged and cataractous lenses. Moreover, dimerization of γS-crystallin significantly increases the protein's propensity to form large insoluble aggregates owing to non-cooperative domain unfolding, as is observed in crystallin variants associated with early-onset cataract. These findings provide insight into how oxidative modification of crystallins contributes to cataract and imply that early-onset and age-related forms of the disease share comparable development pathways. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6fd8.cif.gz | 85.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6fd8.ent.gz | 63.9 KB | Display | PDB format |
PDBx/mmJSON format | 6fd8.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/fd/6fd8 ftp://data.pdbj.org/pub/pdb/validation_reports/fd/6fd8 | HTTPS FTP |
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-Related structure data
Related structure data | 5vh1S S: Starting model for refinement C: citing same article (ref.) |
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Similar structure data | |
Other databases |
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-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
#1: Protein | Mass: 21033.775 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CRYGS, CRYG8 / Production host: Escherichia coli (E. coli) / References: UniProt: P22914 #2: Water | ChemComp-HOH / | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.64 Å3/Da / Density % sol: 53.49 % |
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Crystal grow | Temperature: 292 K / Method: vapor diffusion, sitting drop Details: 0.2 M Sodium tartrate dibasic dihydrate (pH 7.3), 20% w/v polyethylene glycol 3350 |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: Australian Synchrotron / Beamline: MX2 / Wavelength: 0.9763 Å |
Detector | Type: ADSC QUANTUM 315 / Detector: CCD / Date: Jul 15, 2017 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9763 Å / Relative weight: 1 |
Reflection | Resolution: 2.1→43.114 Å / Num. obs: 23548 / % possible obs: 93.6 % / Redundancy: 2.6 % / CC1/2: 0.997 / Rmerge(I) obs: 0.032 / Rpim(I) all: 0.022 / Net I/σ(I): 7.8 |
Reflection shell | Resolution: 2.1→2.2107 Å / Num. unique obs: 2372 / % possible all: 94.35 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 5VH1 Resolution: 2.1→43.114 Å / SU ML: 0.41 / Cross valid method: FREE R-VALUE / σ(F): 1.95 / Phase error: 35.2 / Stereochemistry target values: ML
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.1→43.114 Å
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Refine LS restraints |
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LS refinement shell |
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