2018 Satellite Meeting

Eye Lens Crystallins and the Development of Cataract Disease Workshop

Friday, February 16, 1:00 PM - 5:00 PM
South, Level Three, Room 312 Moscone Center

Pre-Registration is closed. Registration will be accepted on-site

The transparency of the eye lens depends on maintenance of the native state of the Greek key - and crystallins. These proteins define the Greek key fold and have served as models for -sheet proteins. The -crystallin chaperones are the original examples of the small heat shock proteins family and the crystallin system has provided important models for subtrate/chaperone action. The D-crystallins in the central core of the lens, are synthesized during infancy, and are among the longest-lived proteins in the body. Cataract, the leading cause of blindness worldwide, involves the polymerization of covalently damaged or partially unfolded conformations of the lens crystallins into aggregates large enough to scatter visible light. Congenital cataracts are associated with a number of single amino acid substitutions in D-crystallin and other lens crystallins.

The folding, unfolding and aggregation of mutant and modified crystallins have been studied in considerable detail, aided by unusual fluorescence properties of the four buried and conserved tryptophan residues in -crystallins. However the results have not accounted for the development of cataracts in the lens environment. Recent experiments have identified more precisely a) the sites on the protein where oxidative damage results in destabilization b) the potential role of copper and zinc binding in driving aggregation, and c) the identification of sterols that can retard aggregation reactions and are candidates for anti-cataract therapy. The transition from a soluble well-folded -sheet to the polymerized state appears to proceeds through a domain-swapping mechanism. This depends on transient stabilization of a distinctive partially-unfolded -sheet intermediate induced in the mutant or modified protein by temperatures at and above physiological and involves some unexpected thiol chemistry.

Co-Chairs
Jonathan King, MIT
Liliana Quintanar, CINVESTAV, Mexico


Presenters
Jose Antonio Dominguez Calva, CINVESTAV, Mexico
Jason Gestwicki, University of California, San Francisco
Jonathan King, MIT
Kirsten Lampi, Oregon Health Science Center
Rachel Martin, University of California, Irvine
Liliana Quintanar, CINVESTAV, Mexico
Eugene Serebryany, Harvard University


Thanks to the MIT International Science and Technology Initiative for US/Mexico Collaboration, for support of this workshop.