Date Approved

2019

Degree Type

Campus Only Senior Honors Thesis

Department

Chemistry

First Advisor

Dr. Steven K. Backues

Second Advisor

Dr. Hedeel Evans

Third Advisor

Dr. Deborah Heyl-Clegg

Abstract

Autophagy is an important process for the maintenance of proper cell health and function. It is an intricate process which involves the proper coordination of a multitude of specialized proteins, which come together to sequester and degrade cytosolic material. Atgl I is a crucial protein in selective autophagy, a pathway that focuses on the clearance of defunct organelles, protein aggregates, or other pathogenic materials. This pathway is crucial in the prevention of pathologies which involve the buildup of waste in the cell, such as the neurodegenerative diseases, Alzheimer's and Huntington's. Many selective autophagy proteins have been found to have interactions with Atgl 1, leading to the idea of Atgl 1 functioning as a scaffolding protein. In particular, the second coiled-coil domain (CC2) of Atgl 1 has been found to be crucial for Atgl 1 interaction with a variety of partners. To get a better understanding of the exact sites of interactions, we performed a mutagenic screen of the CC2 region, using yeast two-hybrid to monitor the loss of interaction with binding partners Atgl, Atg9, Atgl 1 and Atg32. Through this process we were able to identify two residues, 1562 and Y565, which cause a loss of interaction when mutated. Further investigation has suggested that these residues are crucial for the proper folding of the entire Atg 11 protein.

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