START Lipid/Sterol Binding Domains in Homeodomain Transcription Factors from Plants

Kansas State University, Manhattan KS

Investigators

Abstract

In all multicellular organisms, key regulatory proteins orchestrate the developmental program that defines how specific cell types and tissues are formed. This project will investigate how the regulatory proteins themselves are controlled by interactions with fat molecules. Plants produce a multitude of different fat molecules and other natural products whose molecular functions are not yet understood. The regulatory proteins and fats to be studied in this project are suspected to participate in plant growth control, along with traits that contribute to drought tolerance. Broader impacts of this research will include training of a postdoctoral scholar and several undergraduate students through programs for McNair Scholars, Kansas Louis Stokes Alliance for Minority Participation, and the REU program on Ecology and Evolution in Changing Environments. Public outreach will be accomplished through an educational workshop for teenage girls with interests in STEM careers. The information gained from this research will foster discovery of renewable and sustainable plant-derived products. Interactions between lipid metabolites and proteins are dynamic in all life forms, yet the full extent and biological significance of these interactions is underexplored. Steroidogenic Acute Regulatory (StAR) protein-related lipid Transfer (START) domains belong to an ancient clan of protein motifs characterized by binding to hydrophobic ligands. In plants, START domains occur in homeodomain leucine-zipper (HD-Zip) transcription factors that are master regulators of cell-type differentiation during development. This project addresses the hypothesis that the START domain controls transcription factor activity via ligand binding to a lipid metabolite, linking cell metabolism to gene expression. The overall goal is to identify the natural ligands of HD-Zip-derived START domains. This research will utilize the Arabidopsis model system focusing on class IV HD-Zip transcription factors that are critical for differentiation of the epidermis. Candidate ligands will be identified by protein-metabolite immunoisolation from plant tissues followed by mass spectrometry. Biochemical approaches will be utilized to validate and further characterize protein-metabolite interactions. This project is poised to uncover novel mechanistic insights in understanding the dynamic interplay between metabolic pathways and the regulation of gene expression in the eukaryotes. This project is funded by the Genetic Mechanisms Program in the Division of Molecular and Cellular Biosciences.