Publications

NMR methodology using extreme Carr-Purcell-Meiboom-Gill (eCPMG) experiments to characterize protein dynamics at sub-millisecond timescales. The technique allows investigation of rapid conformational changes in proteins.

The work includes:

• Development and application of eCPMG relaxation dispersion experiments
• Detection of fast protein dynamics at sub-millisecond timescales
• Methodology for studying conformational exchange processes
• Applications to structure-function relationships in biomolecules

The method provides tools to probe rapid protein dynamics and understand how proteins function through conformational changes.

Here we solved the solution structure of the human PALB2 coiled-coil domain using NMR spectroscopy, which form an antiparallel homodimer. We then investigated how missense mutations affect the protein’s fold, homodimerization, and heterodimerization with BRCA1 to provide structural insights into reduced homologous recombination.

Key findings:

• Solution structure of PALB2 coiled-coil domain reveals an antiparallel homodimer
• Analysis of clinically relevant missense mutations and their structural implications
• Correlation between structural disruption and homologous recombination efficiency
• Approach for evaluating variants of uncertain significance in genetic counseling