SASDEZ6: Gamma-crystallin S disulfide-linked dimer (Gamma-crystallin S)

Basic information

• Entry: Database: SASBDB / ID: SASDEZ6

Sample

Gamma-crystallin S disulfide-linked dimer

• Gamma-crystallin S (protein), Homo sapiens

Function / homology

Function:

structural constituent of eye lens / lens development in camera-type eye / visual perception / morphogenesis of an epithelium

Domain/homology:

Beta/Gamma crystallin / : / Crystallins beta and gamma 'Greek key' motif profile. / Beta/gamma crystallins / Beta/gamma crystallin / Gamma-crystallin-like

Component:

Gamma-crystallin S

• Biological species: Homo sapiens (human)
• 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 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.

Contact author

• Aidan Grosas (Australian National University)

Models

• Model #2528: ; Type: dummy / Radius of dummy atoms: 2.25 A / Chi-square value: 1.356 / P-value: 0.648769; Search similar-shape structures of this assembly by Omokage search (details)
• Model #2569: ; Type: atomic / Chi-square value: 4.792; Search similar-shape structures of this assembly by Omokage search (details)

Sample

• Sample: Name: Gamma-crystallin S disulfide-linked dimer / Specimen concentration: 6 mg/ml
• Buffer: Name: 20 mM sodium phosphate / pH: 7

Entity #1339

Type: protein / Description: Gamma-crystallin S / Formula weight: 21.007 / Num. of mol.: 2 / Source: Homo sapiens / References: UniProt: P22914
Sequence:

MSKTGTKITF YEDKNFQGRR YDCDCDCADF HTYLSRCNSI KVEGGTWAVY ERPNFAGYMY ILPQGEYPEY QRWMGLNDRL SSCRAVHLPS GGQYKIQIFE KGDFSGQMYE TTEDCPSIME QFHMREIHSC KVLEGVWIFY ELPNYRGRQY LLDKKEYRKP IDWGAASPAV QSFRRIVE

Experimental information

• Beam: Instrument name: Australian Nuclear Science and Technology Organisation/Australian Centre for Neutron Scattering Bruker Nanostar II; City: Sydney / 国: Australia / Type of source: X-ray in house / Wavelength: 0.1541 Å / Dist. spec. to detc.: 0.73 mm
• Detector: Name: Bruker Hi-Star / Type: multiwire

Scan

Title: Gamma-crystallin S disulfide-linked dimer / Measurement date: Feb 23, 2018 / Storage temperature: 4 °C / Cell temperature: 25 °C / Exposure time: 3600 sec. / Number of frames: 4 / Unit: 1/A /

	Min	Max
Q	0.0135	0.391

Distance distribution function P(R)

Sofotware P(R): GNOM 4.6 / Number of points: 266 /

	Min	Max
Q	0.01387	0.3907
P(R) point	1	266
R	0	75

Result

Type of curve: single_conc

	Experimental	Standard	Standard error	Porod
MW	36 kDa	36 kDa	3.6	28 kDa
Volume	-	-	-	45 nm3

	P(R)	P(R) error	Guinier	Guinier error
Forward scattering, I0	557.7	1	549.21	2
Radius of gyration, Rg	2.44 nm	-	2.352 nm	0.013

	Min	Max
D	-	7.5
Guinier point	5	49