Stability, unfolding, and aggregation of the gamma D and gamma S human eye lens crystallins

The transparency of the human eye lens depends on the properties of the a- crystallin and py-crystallin families of proteins, which accumulate to very high concentrations in mature lens fiber cells. The 0- and y-crystallins are thought to be primarily structural proteins while a-crystallin possess an additional chaperone activity. Aggregation of partially unfolded or covalently damaged forms of these proteins results in cataract, which is the leading cause of blindness in the world. The biochemical basis of the very high crystallin stability, and the nature of the misfolded, modified, or aggregated states, are thus of considerable importance in understanding the etiology of loss of lens transparency. All vertebrate P- and y-crystallins are homologous and contain two highly symmetrical domains with a hydrophobic interface connected by an interdomain linker. The overall sequences, fold topology, and domain interfaces of vertebrate py-crystallins are highly conserved. The two domain 0- and y-crystallins are believed to have evolved by gene duplication and fusion from an ancestral single domain py-crystallin. This thesis is focused on stability and aggregation properties of human yD crystallin (yDwT) and human yS crystallin (ySwT), two of the most abundant proteins in the human lens.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Biology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2007

Author dc:creator

• Mills-Henry, Ishara Amenti Rakem

Advisor dc:contributor.advisor

• Jonathan King.

• Biology.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/38627

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/38627