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Lipid droplets are hub organelles for cellular lipid storage and metabolism. Numerous proteins are recruited to LDs and play critical roles in regulating lipid metabolism. How proteins target to this organelle, however, is just beginning to be understood. The current model postulates that proteins target to LDs either via the endoplasmic reticulum (ER) or directly from the cytosol. I developed cell-free translation and crosslinking assays to biochemically identify the factors that are required for targeting proteins directly from the cytosol to the surface of lipid droplets.

Tail-anchored (TA) proteins contain a single C-terminal transmembrane domain that requires dedicated chaperones for post-translational recognition and targeting. In mammals, the Transmembrane domain Recognition Complex (TRC) proteins have been shown to recognize and target TA substrate to the endoplasmic reticulum. While most TRC factors have been conserved from yeast to humans, Bag6 is a uniquely metazoan component that acts as a triaging factor for its substrates, directing substrates to membranes or to degradation pathways. To understand the molecular basis of Bag6 activity, I determined the molecular architecture of the C-terminal domain of Bag6, which binds two TRC components, TRC35 and Ubl4A. I developed an in vitro biochemical assay to demonstrate that a minimal Bag6 complex comprised of C-terminal domain of Bag6, TRC35 and Ubl4A is sufficient for facilitation of TA targeting. Furthermore, my structural and biochemical work on the Bag6-TRC35 complex revealed a potential mechanism for regulation of nucleocytoplasmic distribution of Bag6.

Shewanella oneidensis MR-1 is a facultative anaerobe that utilizes multiheme cytochrome proteins to carry out unique electron transfer reactions. Shewanella and its cytochromes are considered potential tools for bioremediation and microbial fuel cell development. CymA is a tetraheme cytochrome c for reduction of Fe(III)/Mn(IV) oxides, fumarate, nitrate, nitrite, DMSO and arsenate. It is thought to act as a central hub of electron transfer, accepting electrons from the cytosolic menaquinol pool and transferring them to various periplasmic cytochromes. The details of electron transfer within CymA remain elusive. I generated heme knockout proteins as well as point mutations of putative metal-coordinating residues to parse out the role of individual hemes. My work demonstrated that proper heme incorporation is critical to CymA folding and identified a histidine that modulates the redox potential of CymA.

Undergraduate research assistant in the laboratory of Prof. Hanwoong Lee