Expansion:
Human hnRNP A1, is composed of three major domains: tandem N-terminal RNA Recognition Motifs (RRMs) and a C-terminal intrinsically disordered region. The structural complexity of hnRNP A1 is reflected in its promiscuous nature by which it interacts with various RNA targets. Indeed, hnRNP A1 binds both structured and unstructured RNAs with binding affinities that span several magnitudes.
We employ different structural biology techniques such as NMR spectroscopy, X-ray crystallography and SAXS to characterize the mechanisms by which hnRNP A1 interacts with its diverse RNA targets. We also use isothermal titration calorimetry (ITC) and differential scanning fluorimetry (DSF) to measure protein-RNA affinity, thermodynamics of nucleic acid binding and stability. We perform molecular dynamic (MD) simulations to model short and long-range hnRNPA1 interdomain communications. Finally, we attempt to interpret our biophysical data in biological context by testing hnRNPA1 in cellular assays.
