Michael Latham

Seminar Details

Host: Dr. Jae Hyun Cho

Time: 4:00 pm-5:00 pm

Location: BICH 108

Seminar Abstract

Macromolecular complexes that bind nucleic acids are central to nearly all cellular processes, from DNA repair to gene regulation. The function of these assemblies is often dictated by complex structural dynamics and long-range allosteric communication. Our laboratory leverages NMR spectroscopy to characterize the structure, dynamics, and function of these challenging systems. In this seminar, I will present our recent work on two distinct protein-nucleic acid complexes. 

First, I will discuss the interaction between DNA and the functional amyloid CRES, a protein essential for male fertility. We have determined the structural basis for the CRES-DNA interaction, identifying a positively charged interface on the CRES amyloid fibril that engages DNA. Using a suite of NMR experiments, we show that DNA binding induces a dynamic protein coat around the DNA which regulates the kinetics of CRES amyloid assembly. These results provide a mechanism for how DNA binding modulates the biophysical properties of a functional amyloid. 

Second, I will present ongoing studies of the Mre11-Rad50 (MR) complex, a central enzyme in the DNA double-strand break repair pathway. The MR complex must coordinate the nuclease activity of Mre11 with the ATP hydrolysis cycle of Rad50 across large distances. Using methyl-based NMR experiments, we are mapping the allosteric pathways that connect the DNA- and ATP-binding sites to the nuclease active site and beyond. Our results support a dynamic communication network that coordinates the enzymatic activities of the complex.