BYU

Abstract by Theresa Smith

Personal Infomation


Presenter's Name

Theresa Smith

Degree Level

Doctorate

Abstract Infomation


Department

Chemistry and Biochemistry

Faculty Advisor

Barry Willardson

Title

The Role of the Cytosolic Chaperonin CCT in folding RPE65

Abstract

The process by which all-trans retinal is converted back to 11-cis retinal following light absorption by rhodopsin is known as the visual cycle and is necessary to sustain vision. A key protein in this process is the retinoid isomerase, RPE65. Mutations in RPE65 impair the visual cycle and can cause severe retinal degenerative diseases such as Leber Congenital Amaurosis (LCA), however little is known about how it is folded or how mutations disrupt its function. We have evidence that RPE65 is a substrate of the cytosolic chaperonin CCT. CCT interacts with both WT RPE65 and several pathogenic mutants and RPE65 expression is significantly decreased upon CCT knockdown.  Furthermore, we purified a complex of both proteins and have currently solved the cryo-EM structure to 4.2 angstroms, which shows a mass attributable to RPE65 imbedded within CCT. Improvement of this structure and further characterization of the relationship between RPE65 and CCT will provide a basis for developing structure based therapies for LCA.