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Aging and Stability in Extremely Long-Lived Proteins

The optical power of the vertebrate eye lens is generated by the crystallins, exceptionally soluble proteins that are packed in at very high concentration (up to about 50% protein in humans, and even higher in fish). The structural and refractive crystallins of vertebrates have evolved from an ancient cation-binding fold, mostly losing their affinity for metal ions in the process. The extraordinary solubility of these proteins is even more remarkable given that the lens has almost no protein turnover: crystallin proteins have to last for a lifetime. When crystallins do aggregate, the result is cataract, a major cause of blindness worldwide.  I will present our recent structural and biophysical work on lens protein optical properties, mutations involved in hereditary cataract, the impact of oxidative damage, and the complex relationship among different types of post-translational modifications. Crystallin damage not only contributes to protein precipitation leading to cataract, but also impacts the refractive function of these proteins. I will also discuss the NMR instrumentation we have developed to study semi-solid protein systems of this type that are not amenable to either standard solid-state or solution techniques.

 

Seminar Host
Matthias Heyden
Seminar Speaker
Rachel Martin
Seminar Speaker Affiliation
UC Irvine-Dept of Chemistry/Molecular Biology & Biochemistry
Seminar Date
Seminar Semester
Fall