Junji Iwahara, PhD
Professor, Department of Biochemistry & Molecular Biology
Tel: (409) 747-1403
Fax: (409) 772-6334
Campus Location: 5.104C Medical Research Bldg
Pubmed Publications | Lab Webpage
Our research field is biophysical chemistry of proteins, DNA, and their interactions.
In life, complex networks of molecular interactions involve electrostatic forces that influence structure and function of biological macromolecules.
Electrostatics is important for our fundamental understanding of biomolecular functions as well as for drug development. Biomolecular electrostatics has been a subject of computational investigations based on 3D structures. Our nuclear magnetic resonance
(NMR) methods are changing this situation. These solution NMR methods allow us to quantitatively investigate biomolecular electrostatics without any use of structure information.
Macromolecular binding event is not simply a two-state exchange between free and bound states. In fact, previous kinetic investigations have suggested that the process of the specific complex formation goes through intermediate states called as
target search or encounter complexes and the presence of such intermediates greatly accelerates the overall process. In terms of structure, how do individual components bind to each other at the intermediates states? How dynamic are they? These are
fundamentally important questions for understanding macromolecular recognitions, while structural biology has not given adequate answers yet. It is because the very low population at equilibrium and dynamic nature of such states make the investigations
extremely difficult. We have developed a number of powerful NMR methods that permit characterization of the intermediates in macromolecular binding at equilibrium. Applying the new techniques, we investigate structural and dynamic aspects of binding
intermediates. Currently, the focus in our research is on the target search process whereby gene-regulatory proteins are able to efficiently and rapidly locate their specific DNA target sequence in a sea of non-specific DNA.
HMGB1 is a very interesting DNA-binding protein that plays important roles in the cell nuclei and in extracellular space. HMGB1 typically exists in the cell nuclei and serves as a DNA chaperone and assists various other DNA-binding proteins. HMGB1 contains two DNA-binding domains and intrinsically disordered regions (IDRs). HMGB1 recognizes atypical DNA such as Holliday junction, bulged DNA, cisplatin-modified DNA, and G-quadruplex. HMGB1 is released to extracellular space not only passively from dying cells, but also actively from platelets and some healthy cells. Extracellular HMGB1 serves as a danger signal and plays several important roles in innate immunity involving extracellular DNA related to infection or tissue damage. HMGB1 is involved in many inflammatory diseases and has been regarded as a potential therapeutic target. Using NMR spectroscopy, fluorescence spectroscopy, and other techniques, we are characterizing HMGB1 and trying to find effective ways for HMGB1 inhibition.