Date of Graduation

8-2017

Document Type

Thesis

Degree Name

Master of Science in Cell & Molecular Biology (MS)

Degree Level

Graduate

Department

Biological Sciences

Advisor/Mentor

Paul Adams

Committee Member

Josh Sakon

Second Committee Member

Mack Ivey

Keywords

Molecular features, TSC2-218-N119K

Abstract

Structure-function relationships of any complex underlie the molecular details of the biological interactions. Rheb, Ras Homology Enriched in Brain, is a Ras-related protein, and it is genetically identified as a molecular switch. Rheb is regulated by cycling between the biologically active GTP and inactive GDP-bound forms. This regulation is partially controlled by an interaction with Tuberous Sclerosis Complex2 (TSC2), a GTPase activating protein (GAP). Upon interaction, TSC2 stimulates Rheb GTP hydrolysis and diminishes the mammalian target of rapamycin (mTOR) pathway. The mTOR pathway is involved in proteins synthesis, cell cycle, and signaling. Mutation in TSC2 causes abnormal activation of Rheb and affects the mTOR pathway signaling. However, the molecular details of this interaction are still largely unidentified. The goal of this project is to characterize the molecular features of TSC2-218-N119K interaction by using biochemical and biophysical methods. The long-term objectives are to fill the gap in understanding TSC2-Rheb interaction, TSC2 GAP mechanism, and how that affects the mTOR pathway.

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