Hello from the Latham Lab at Texas Tech University! Our research program focuses on understanding the interplay of protein structure, dynamics, and function, particularly in large macromolecular assemblies. Our current emphasis is the characterization of an essential protein complex that recognizes double-strand breaks in our DNA. Failure to repair this damaged DNA can lead to mutations and has been implicated in a variety of cancer types. To accomplish our goals, we utilize sophisticated solution state NMR spectroscopy techniques, which allow us to probe changes in protein structure and dynamics that occur as part of the functional cycle of the complex as well as changes that occur upon mutation of the complex. We couple this information with biochemical activity assays and in cell experiments, which report on function. Together, these data will provide a framework for understanding how changes in structure and dynamics of a protein complex choreograph complex functions.
Nuclear magnetic resonance (NMR) spectroscopy is a technique to study the structure and motions of molecules. Solution state biomolecular NMR focuses these methods on the molecules that are important for life and has been used to derive the structures of many important proteins, nucleic acids (DNA and RNA), and multi-subunit complexes.
Structural biology combines biophysics, biochemistry, and molecular biology to study the molecular structure of biological macromolecules. Its particular goals are to determine how proteins and nucleic acids acquire the structures they have and how alterations in their structures affect their function.
Proteins are not strictly static objects, but can populate ensembles of conformations in solution. Transitions between these states occur on a variety of length and time scales, and have been linked to functionally relevant processes such as allosteric signaling and enzyme catalysis. NMR is uniquely suited to detect and measure these dynamics.
DNA repair is a collection of processes by which a cell identifies and corrects damage to its DNA molecules. There are different pathways (protein cascades) of repair depending on the type of damage, and therefore the type of repair required. Some proteins involved in these cascades are dynamic as they detect and repair DNA damage.