RIG: Mechanisms of Molecular Recognition by the Transcription Factor LMO7 at the Nuclear Envelope and the Adherens Junctions

Southern Illinois University At Carbondale, Carbondale IL

Investigators

Abstract

LMO7 is a transcription factor that has two distinct roles. At the nucleus it regulates the transcription of genes important for heart, muscle and retina formation. It also plays an adaptor role in stabilizing communication between proteins (cadherin and nectin) that are involved in cell-to-cell junctions. This project will determine at the molecular level 1) the structure-function relationships associated with the recognition processes of two conserved structural domains (PDZ and LIM) within LMO7, and 2) how variations in these domains influence the two functions (adaptor and transcriptional regulator) of the LMO7 protein. Nuclear Magnetic Resonance (NMR) spectroscopy, molecular biological, biochemical and biophysical methods will be employed to understand specific interactions and the dynamic structural changes that occur upon binding. Results from the atomic level high-resolution structures will provide information for the design of mutagenesis experiments that will advance our understanding of the protein-protein assembly process. These studies will define the differences and similarities between the interactions that are relevant to multi-molecular assembly within the cadherin-nectin containing complexes, as compared to those interactions required for the regulation of gene transcription in the nucleus. Broader Impacts This project will provide graduate, undergraduate and high school students the opportunity to participate in structural biology research on the structure of proteins, the regulation of gene expression, and specific mechanisms of molecular recognition. A special emphasis will be placed on the recruitment to this project of students from economically disadvantaged backgrounds as well as members of minorities under-represented in scientific research. High school students will be mentored through a Project SEED program of the American Chemical Society. Aspects of this project will be integrated into courses at both graduate and undergraduate levels, and students involved in this research will have the opportunity to present their results at regional and national conferences.