Role of RUS Proteins in Vitamin B6 Homeostasis Regulation
Ramit Guha
Department of Biology
Faculty Supervisor: Zheng-Hui He
Vitamin B₆, in its active form pyridoxal 5′-phosphate (PLP), is an essential yet highly reactive cofactor required for more than 140 enzymatic reactions. Cells must carefully regulate PLP availability to balance metabolic demand with protection against cytotoxicity. In Arabidopsis thaliana, ROOT UV-B SENSITIVE 1 (RUS1) and ROOT UV-B SENSITIVE 2 (RUS2) are DUF647-containing proteins required for vitamin B₆ homeostasis. Mutants lacking RUS function display PLP-deficiency phenotypes despite normal total vitamer levels, suggesting a defect in PLP mobilization rather than synthesis. My project investigates whether RUS1 and RUS2 directly bind PLP and regulate its intracellular distribution. Using structural modeling, molecular docking, and biochemical validation, I aim to define the molecular mechanism by which RUS proteins capture and stabilize PLP. This work will establish how membrane-associated protein complexes coordinate cofactor trafficking, providing new insight into vitamin B₆ regulation and broader principles of metabolic homeostasis.