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In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
Published on: August 20, 2019
Matrix bound SFD mutant TIMP-3 is more stable than wild type TIMP-3
Mohammed A Majid1, Valerie A Smith, Andrew C Newby
1Bristol Eye Hospital, Lower Maudlin Street, Bristol BS1 2LX, UK.
The British Journal of Ophthalmology
|March 27, 2007
Summary
Matrix-bound Sorsby's fundus dystrophy (SFD) mutant TIMP-3 proteins are more stable than wild-type. This enhanced stability of mutant TIMP-3 may explain the early onset of SFD.
Area of Science:
- Ophthalmology
- Genetics
- Biochemistry
Background:
- Sorsby's fundus dystrophy (SFD) is a degenerative retinopathy.
- SFD involves the accumulation of mutant TIMP-3 protein in Bruch's membrane.
Purpose of the Study:
- To compare the stability of matrix-bound SFD mutant TIMP-3 proteins with wild-type TIMP-3.
- Investigate the thermodynamic properties of mutant TIMP-3 in SFD.
Main Methods:
- COS-7 cells were transfected with wild-type or SFD mutant TIMP-3 cDNA.
- Matrix-bound TIMP-3 was quantified using ELISA.
- Protein denaturation was assessed by heating to 100°C and monitored by reverse zymography.
Main Results:
- Matrix-bound SFD mutant TIMP-3 retained biological activity after 24 hours at 100°C.
- Wild-type TIMP-3 lost biological activity within 6 hours at 100°C.
- SFD mutant TIMP-3 demonstrated significantly greater thermal stability.
Conclusions:
- Matrix-bound SFD mutant TIMP-3 proteins are thermodynamically more stable than wild-type.
- This enhanced stability offers a potential explanation for the earlier onset of SFD compared to age-related macular degeneration.
